Journal of Cancer Immunology

Original Research Open Access

Role of Exogenous HSPA1A in Cytokine Regulation Through TLR2, TLR4, TLR5, TLR7, and MyD88/MAPK p38/NF-κB Pathways in Differentiated THP-1 Cells

Nusrat Jahan Hoque, Emmanuel Ogbodo, Rajah Khaouader Essalemi, Chelsea R Wood, Hend Moosa

Heat shock proteins (HSPs) are ubiquitous proteins that play an important role in cellular stress responses, contributing to immune activation through interactions with toll-like receptors (TLRs) and other pattern recognition receptors. Despite extensive research, the exact mechanism by which HSPs modulate immune responses is still unclear. This study explores the immune-modulatory role of HSPA1A by examining its effect on cytokine production in PMA-differentiated THP-1 macrophages, preincubated with TLR-specific blocking peptides prior to exposure to recombinant HSPA1A.

Original Research Open Access

Role of Exogenous HSPB1 in Cytokine Regulation Through TLR2, TLR4, TLR5, TLR7, and MyD88/MAPK p38/NF-κB Pathways in Differentiated THP-1 Cells

Rajah Khaouader Essalemi, Emmanuel Ogbodo, Nusrat Jahan Hoque, Chelsea R Wood, Hend Moosa

The modulation of the innate immune system has been a significant area of interest in research, as it represents the body’s first line of defense against pathogens. Heat shock proteins (HSPs), particularly small HSP, like HSPB1 (HSP27), are emerging as potent therapeutic options for preventing and managing inflammatory conditions due to their ability to modulate the immune system. 

Commentary Open Access

Epigenetic Reprogramming with DNMT Inhibitors: A Multi-Mechanistic Approach to Enhance Immunotherapy in Glioblastoma

Thomas J. Lai, Robert M. Prins, Richard G. Everson

Although adoptive T cell therapies and immune checkpoint blockades have been successfully implemented in various cancers, no immunotherapy agents have yet reached FDA approval for glioblastoma (GBM). GBM harbors a uniquely immunosuppressive tumor microenvironment that presents significant barriers to effective immunotherapy. Key hallmarks of the GBM microenvironment include the exclusion of lymphoid cells from the tumor core and the predominance of immunosuppressive tumor-associated macrophages .

Commentary Open Access

Sexual Dimorphism in Immunity and Metabolism: Unraveling the Impact on Response to Cancer Immunotherapy

Adam C. Soloff, Hannah M. Udoh, Charles E. Bardawil, Xinyue Zhao, Laura P. Stabile

A recent observational study by Jin et al., found male sex and pretreatment weight loss to be associated with worse progression free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibition (ICI) [1]. Although sexual dimorphism in immunity is well established, recent studies have begun to elucidate the mechanisms by which sex-specific immunity contributes to diseases such as cancer, and autoimmunity [2-5]. Similarly, the complex interplay between gonadal hormones, sex-based gene expression, and metabolism, particularly immunometabolism and the subsequent ability to mount effective antitumor immunity is a burgeoning field of investigation.

Review Article Open Access

Mechanisms and Clinical Implications of Immune Checkpoint Inhibitors PD-1, CTLA-4, and TIM-3 in Cancer

Jordan T. Bruner, Joseph D. Cozis, Austin J. Marrah, Trent G. Mayberry, Braydon B. Cowan, Mark R. Wakefield, Yujiang Fang

Cancer poses a significant health challenge due to its complex nature and the limitations of current treatments. Over the last decade, emerging research has identified that modulation of immune checkpoint molecules such as CTLA-4, PD-1, and TIM-3 can have potential therapeutic benefits. These molecules are critical regulators of the immune system’s ability to target and eliminate cancer cells. This review explores the roles of these immune checkpoints in cancer and hematological malignancies; examining their mechanisms of action and the potential they hold for enhancing therapeutic outcomes.

Mini Review Open Access

Immunotherapy in MSS/pMMR Metastatic Colorectal Cancer – Insights from the KEYNOTE-651

Ruoyu Miao, Richard D. Kim

Microsatellite stable (MSS)/mismatch repair-proficient (pMMR) colorectal cancer (CRC) accounts for the majority of CRC cases and generally respond poorly to immunotherapy alone. This mini-review integrates findings from the KEYNOTE-651 study with current knowledge of frontline immunotherapy in MSS/pMMR metastatic CRC and explores the implications for clinical practice and future research directions.

Original Research Open Access

Exogenous Heat Shock Proteins HSPA1A and HSPB1 Interact with TLR2, TLR4, TLR5, and TLR7 on Differentiated U937 Monocytic Cells

Emmanuel Ogbodo, Francesco Michelangeli, John H.H. Williams

Biological cells are sensitive to both pathological and non-pathological stress, which can activate the innate immune response. This activation often involves the release of heat shock proteins (HSPs), such as HSPA1A and HSPB1. However, the implications and relationships between HSP release and immune system activation remain unclear. While evidence suggests that HSPs play a role in immune system activation and regulation, their immune regulatory characteristics are still debated.

Commentary Open Access

Beyond the Mutation: A Closer Look at Birt-Hogg-Dubé Syndrome

Alamin Alkundi, Basma Bakhiet

This commentary aims to delve into the diagnostic challenges associated with Birt-Hogg-Dubé (BHD) syndrome, as outlined in the BMJ case report titled “A Case of Phaeochromocytoma in a Female Patient with Phenotypical Expressions for the Rare Birt-Hogg-Dubé (BHD) Syndrome” (doi:10.1136/bcr-2022- 252362). BHD syndrome is a rare genetic disorder that is inherited in an autosomal dominant manner and is caused by mutations in the FLCN gene on chromosome.

Commentary Open Access

Effects of Tumor-derived Small Extracellular Vesicles on T cell Survival in Patients with Cancer; A Commentary

Theresa L. Whiteside

Tumor-induced immune suppression has been recognized as one of the major barriers for cancer immune therapies, including checkpoint inhibitors. Immunosuppressive mechanisms that tumors utilize to silence anti-tumor immune cells are numerous and differ between tumor types. 

Mini Review Open Access

Tolerogenic De-liver-y: Glycopolymer-mediated Approaches to Induce Antigen-specific Tolerance

Ian Christopher McKnight, Stephane Lajoie, David Scott Wilson

Numerous autoimmune diseases, which currently affect a sizable portion of the global population, are driven by aberrant autoantigen-specific T cell responses that result in tissue destruction and loss of function. Current therapeutics for autoimmunity are non-curative and rely on global immunosuppression, leaving patients vulnerable to opportunistic infections and malignancies. An ideal approach would suppress autoantigen-specific T cell responses while leaving the remainder of the immune system intact

Commentary Open Access

A Blood-based Metabolite Signature for Personalized Risk Assessment of Pancreatic Cancer

Ricardo A León-Letelier, Yihui Chen, Riccardo Ballaro, Ehsan Irajizad, Kim-An Do, Anirban Maitra, Jianjun Zhang, C Max Schmidt, Johannes F. Fahrmann

Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related deaths in the United States. Modeling studies project PDAC to be the second leading cause of cancer-related mortality by 2040. Poor survival rates are attributed to the overwhelming majority (>80%) of patients presenting with locally advanced or metastatic disease, which precludes surgical resection and possibility of a long-term cure. 

Mini Review Open Access

Phosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy

Apoorvi Tyagi, Yury Patskovsky, Iryna Voloshyna, Michelle Krogsgaard

Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumor-specific antigens and offer promising avenues for targeted anti- cancer therapies. In this review, we focus on the role of phosphorylated peptides (p-peptides) in cancer immunity.

Commentary Open Access

Commentary: On the Emerging Role of Innate Lymphoid Cells in Bladder Cancer

Zaineb Hassouneh, Gang Huang, Nu Zhang, Manjeet Rao, Neelam Mukherjee

In the evolving landscape of bladder cancer (BCa) immunotherapy, this commentary offers a critical and timely reflection on a recent review that we published previously on targeting innate lymphoid cells (ILCs) in BCa. Even though BCa immunotherapy has traditionally focused on enhancing T-cell responses, the review explores the promising but underappreciated role of ILCs in BCa. From natural killer cells to the diverse ILC subtypes, these cells offer a dualistic impact on tumor progression and immune surveillance.

Commentary Open Access

A New Study Uncovering the Cause of Health Deterioration and Mortality in Late-stage Cancer Patients

Lingbing Zhang

Cachexia [Greek origin, Etymology: kakos (bad) and hexes (condition)] is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle mass with or without loss of body fat. This syndrome can be linked to anorexia, inflammation, insulin resistance, and raised protein turnover. Cachexia is typically found to be associated with severe disorders such as chronic heart/renal failure, cancer, and autoimmune diseases. This condition results in deprived nutrition and decreased skeletal muscle mass. 

Commentary Open Access

Commentary: Next Generation Sequencing (NGS) of Matched Tissue and Circulating DNA (ctDNA) in Patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Panagiota Economopoulou, Ioannis Kotsantis, Amanda Psyrri

Despite advances in multimodality treatment, a significant proportion of patients with squamous cell carcinoma of the head and neck (SCCHN) eventually presents with either local recurrence or distant metastases. Although imaging and tissue biopsy are the cornerstones for the diagnosis of relapse, tissue acquisition is impeded by the complex anatomy of head and neck tumors which frequently necessitates open biopsies via examination under anesthesia; therefore, understanding the underlying molecular biology is challenging. 

Review Article Open Access

Cancer and Immune System: A Comprehensive Analysis of the General Patterns of Carcinogenesis

Oleksandr Shevchenko, Volodymyr Shevchenko

The proposed review reveals the pathogenesis of the malignant tumor process and the patterns of its initiation and development. It was established that the basis of the malignant tumor process is the physiological process of implantation of the embryo in the thickness of the decidual membrane of the uterus and the regulation of the invasive function of the trophoblast, created by evolution.

Review Article Open Access

Role of PD-L1 SP263 Assay in Cancer Immunotherapy: A Comprehensive Review

Trupti Pai, Hema Malini Aiyer, Bijal Kulkarni, Vidya MN, Shashikant C.U. Patne, Sandeep Sewlikar, Jayesh Deshmukh

Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for many types of cancers, leading to significant improvements in patient survival. Treatments like nivolumab, pembrolizumab, durvalumab, and atezolizumab have shown remarkable efficacy. Among the various biomarkers used to guide ICI therapy, PD-L1 is one of the most extensively studied. The PD-L1 SP263 assay is one of the most commonly used assays for identifying PD-L1 status.

Commentary Open Access

A Paradoxical AKT: Exploring the Promise and Challenges of PI3K/AKT/mTOR Targeted Therapies

Gennie L. Parkman, Sheri L. Holmen

Cutaneous melanoma, a malignancy originating from melanocytes in the skin, is challenging to treat due to its aggressive nature and propensity to metastasize. Despite the advancement of multifaceted treatment interventions, including targeted therapy, immunotherapy, and cellular therapy, the five-year-survival for patients with stage IV melanoma is only ~30% [1-3]. BRAF activating mutations are the most common genetic alteration in melanoma, comprising ~50% of all cutaneous melanoma cases [4,5]. 

Mini Review Open Access

Tertiary Prevention and Treatment for Reducing Leukemia Relapse

Nikita Manyak, Mingyi Chen, Su Yon Jung

We have found little available information in the medical literature on the prevention and treatment of tertiary leukemia or patients' prognosis. We thus conducted a comprehensive literature review using the most recently updated American Society of Hematology guidelines, searching the MEDLINE and PubMed electronic databases by using the key term "progression-free survival (PFS) leukemia" and restricting results to the English language within the last decade.

Mini Review Open Access

Combining EGFR and KRAS G12C Inhibitors for KRAS G12C Mutated Advanced Colorectal Cancer

Hirotaka Miyashita, David S. Hong

KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation.

Commentary Open Access

Commentary on the Volume-Outcome Relationship in CRS/HIPEC for Peritoneal Carcinomatosis

Stephanie N Gregory, Praveen D Chatani, Henry A Pitt, H Richard Alexander

Peritoneal carcinomatosis historically has a poor prognosis; however, Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have shown improved outcomes. While a volume-outcome relationship is established in oncologic surgeries, its applicability to CRS/HIPEC remains unexplored. This study examines the impact of hospital volume on CRS/HIPEC outcomes.

Commentary Open Access

Unlocking Biomarkers for Cancer Immunotherapy: Immune Monitoring with High-Parameter Flow Cytometry

Xiyu Peng, Fiona Ehrich, Ronglai Shen, Panageas Katherine

A decade ago, Science magazine named cancer immunotherapy as the breakthrough of the year, recognizing its pivotal clinical trials of antibodies designed to inhibit negative regulators of T cell function. Antibody therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell protein 1 (PD-1) initially showed effectiveness against advanced melanoma and have since expanded in use to non-small cell lung, renal cell, and bladder cancers, among others. 

Mini Review Open Access

AMBRA1: Orchestrating Cell Cycle Control and Autophagy for Cellular Homeostasis

Yang Wang, Goran Stjepanovic

The Activating Molecule in Beclin-1-Regulated Autophagy (AMBRA1) is a scaffold protein involved in many cellular processes, including autophagy, apoptosis, cell growth and development. AMBRA1 functions as a substrate receptor of the DDB1-Cullin4-RBX1 ubiquitin E3 ligase complex that plays key roles in autophagy and the cell cycle regulatory network. Considering the crucial role of AMBRA1 in cellular homeostasis, structural and functional studies are important for understanding the mechanisms that coordinate these cell responses.

Commentary Open Access

Aromatase Inhibitors and their Connection to Autoimmunity

Savannah Bowman, Carlos H Barcenas, Huifang Lu

The aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane are often prescribed as endocrine therapy for patients with estrogen receptor–positive breast cancer. AIs are associated with musculoskeletal side effects such as bone loss, arthralgias, myalgias, and tenosynovitis. Notably, exemestane is a steroidal AI and both anastrozole and letrozole are non-steroidal AIs. 

Research Article Open Access

Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer

Chethan Ramamurthy, Karen M. Wheeler, Shaun Trecarten, Zaineb Hassouneh, Niannian Ji, Yifen Lee, Robert S. Svatek, Neelam Mukherjee

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration—neoadjuvant or adjuvant—remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. 

Commentary Open Access

Enhancing the Efficacy of CAR-T Cell Therapy: A Comprehensive Exploration of Cellular Strategies and Molecular Dynamics

Mehmet A. Baysal, Abhijit Chakraborty, Apostolia M. Tsimberidou

The emergence of chimeric antigen receptor T cell (CAR-T cell) therapy has revolutionized cancer treatment, particularly for hematologic malignancies. This commentary discusses developments in CAR-T cell therapy, focusing on the molecular mechanisms governing T cell fate and differentiation. Transcriptional and epigenetic factors play a pivotal role in determining the specificity, effectiveness, and durability of CAR-T cell therapy.

Editorial Open Access

Role of a Training Simulator for Kidney Biopsy and Tumor Removal Procedures in Complex Positioning Scenarios: The Key Challenges

Trijit Reet Adhikary, Santu Paul, Anu Jayanthi Panicker, Sarada Prasad Dakua

Preventable medical errors and iatrogenic injuries remain significant contributors to mortality and morbidity, emphasizing the need for effective clinical training methodologies. Traditional teaching methods often inadequately prepare physicians for mastering procedural skills. Surgical procedures like nephrectomy for kidney tumor removal require intricate understanding of renal anatomy and meticulous technique. Close coordination among the specialists remains crucial to ensure optimal patient outcomes.

Review Article Open Access

The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers

John Pfail, Jake Drobner, Krishna Doppalapudi, Biren Saraiya, Vignesh T. Packiam, Saum Ghodoussipour

The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome’s role in modulating and predicting immunotherapy response to genitourinary malignancies.

Research Article Open Access

Prognostic Factors of Nintedanib-docetaxel in Patients with Previously Treated Non-small-cell Lung Cancer

Luis Cabezón-Gutiérrez, Sara Custodio-Cabello, Vilma Pacheco-Barcia, Magda Palka-Kotlowska, Catalina Saez-Bertrand, Marta Blasco-Guerrero

Background: In advanced non-small-cell lung cancer (NSCLC), second-line treatment with nintedanib plus docetaxel improves survival compared with docetaxel, especially in patients with adenocarcinoma histology who progressed within 9 months after the start of firstline treatment. It is therefore necessary to identify new biomarkers/prognostic factors that select the patients who benefit from this type of treatment.

Review Article Open Access

Emulating the Role of Neutrophils in Head and Neck Cancer Microenvironment: Prognostic Role and Therapeutic Strategies

Khushwant Singh, Pramod kumar Gautam

Head and neck squamous cell carcinoma (HNSCC) are a group of cancers that affect various parts of the head and neck, such as the lip, oral cavity, oropharynx, hypopharynx, and nasopharynx. In India, it accounts for approximately 30–40% of all cancers, while in the United States, it represents around 4% of all cancer cases. HNSCC is a significant contributor to cancer-related deaths globally. While smoking is linked to HNSCC

Review Article Open Access

Epithelial Mesenchymal Transition: The Ultimate Driver of Cancer on Difficult Paths

Devavrat Tripathi, Pramod Kumar Gupta, Savita Kulkarni

Metastasis is the perilous aspect of cancer and is responsible for 90% of deaths due to cancer. It represents an enigmatic and complex biological cascade that is poorly understood. The constant development in cancer research and the advent of new principles in metastasis have discovered some of the molecular keystones like epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) of this cascade.

Research Article Open Access

Negative Feedback Expansion of Tregs Caused by Endogenous IL-2 Limits the Activity of IL-2-based Therapies

Inbar Amit, Natalie Levitin, Meital Gadrich, May Ben-Mayor, Timothy Wyant, Reut Barak, Liron Danielpur, Morya Ifrach, Itzhak Meir, Olga Bluvshtein, Yehezkel Sasson, Sharon Fischman, Guy Nimrod, Michael Zhenin, Yair Fastman, James Vasselli, Aron Knickerbocker, Ronald Herbst, Yanay Ofran

Stimulating effector T-cells (Teffs) without inducing regulatory T-cells (Tregs) has been the primary goal of IL-2-based therapies for cancer. Recently, modified IL-2 designed for differential T-cell expansion for the treatment of cancer has failed in the clinic. We propose that treatments based on exogenous administrations of modified IL-2 are inherently undermined by a negative feedback loop, caused by IL-2 secreted endogenously from activated effector T-cells.

Review Article Open Access

Insights from Long Noncoding RNAs into Cancer-immunity Cycle Regulation

Ye-Lin Liang, Yuan Zhang, Xi-Rong Tan, Han Qiao, Jun Ma, Ying-Qin Li, Na Liu

Accumulating evidence from recent research offers new perspectives on the functions of long non-coding RNAs (lncRNAs) in immunooncology. In addition to modulating the aggressiveness of cancer cells, lncRNAs are essential players in regulating various immune cells and stromal cells, playing a role in reshaping the tumor microenvironment and affecting anti-tumor immunity.

Commentary Open Access

Early Integration of Palliative Care for Patients Receiving Systemic Immunotherapy for Renal Cell Carcinoma

Megan Stout, Akshay Thaper, Vivien Xu, Eric A. Singer, Biren Saraiya

Palliative care (PC) aims to prioritize the quality of life and comfort of those with complex and terminal illnesses through the physical, psychological, social, and spiritual needs of the individual. Palliative care can support individuals from the day of their cancer diagnosis through end-of-life and bereavement

Editorial Open Access

Role of Liver Navigation in Surgery Planning and the Challenges

Sarada Prasad Dakua, Sagnika Dash, Sagarika Pati, Julien Abinahed

With continuous advancement of high dimensional imaging devices and the development of new image computing and visualization techniques, the world of interventional radiology and surgical care has achieved new heights. Computer vision and image processing plays an important role in health care, such as analysis, visualization, and exploration of medical image data.

Commentary Open Access

A Surprising Benefit of Cysteine Capping for Antibody Drug Conjugates

Aaron M. D’Antona, Kaushik Dutta, Xiaotian Zhong

Antibody-drug conjugates (ADCs), combining the best features of monoclonal antibodies and small molecule drugs, are considered the “guided missiles” for cancer therapy, with eleven FDA-approved products. Yet the ADC modality still presents a huge challenge to drug developers, especially for targeting tumors with low abundance and/or heterogeneity of tumor-associated antigens.

Perspective Open Access

Molecular Iodine Misconceptions: A Novel Formulation Approach to Topical Iodine

Jack Kessler

My team of chemists have formulated molecular iodine (I2) so it can be studied independent of other iodine species.The initial impetus for this effort was to allow for a higher concentration of biocidal I2 that would not evaporate into the atmosphere when applied to skin.

Commentary Open Access

Clutch Control: Changing the Speed and Direction of CAR-T Cell Therapy

Alberto Nobili, Aya Kobayashi, Patrick C. Gedeon, Carl D. Novina

The adoptive transfer of T cells expressing chimeric antigen receptors (CAR-T cells) has revolutionized the treatment of hematological malignancies, providing unmatched clinical responses in adults and children with relapsed or refractory B cell malignancies.

Review Article Open Access

Performance of the Tyrer-Cuzick 8 Breast Cancer Risk Model Across Races: A Review

Melissa D Porterhouse, Rosalinda Alvarado

The Tyrer-Cuzick (TC) model is a breast cancer risk assessment tool that provides women with their risk of developing breast cancer based on genetic and personal factors. The most recent version of the TC model, TC8, is the first version to include breast density as a risk factor for breast cancer.

Commentary Open Access

Can Butein be a Future Candidate for the Treatment of Advance Metastatic Thyroid Cancer?

Devavrat Tripathi, Savita Kulkarni

The incidence and prevalence of papillary thyroid cancer (PTC) are increasing worldwide and it is the 5th most common endocrine cancer in females.

Review Article Open Access

Higher Frequency and Poor Prognosis with COVID-19 Associated Cytokine Storm among Cancer Patients: Between Two Fires

Murat Bektaş, Nevzat Koca, Burak İnce

At the end of 2019, the world faced a new disease, COVID-19 caused by SARS-Cov-2 and became a pandemic within few weeks. The fact that COVID-19 spreads very quickly and has
significant morbidity and mortality had devastating effects all over the world.

Commentary Open Access

OGR1-a Novel Modulator Target of Tumor Immunotherapy

Guoxin Zhang, Ran Gao

Tumors mainly utilize glucose to promote aerobic glycolysis for their survival (Warburg effect). The highly glycolytic environment is not suitable for the survival and function of effector T cells, and leads to the decline of antitumor immunity.

Review Article Open Access

Emerging Potential of Plant Virus Nanoparticles (PVNPs) in Anticancer Immunotherapies

Mehdi Shahgolzari, Steven Fiering

Plant virus nanoparticles (PVNPs) are increasingly recognized and studied for use in biomedical applications. PVNPs include plant virions with self-assembled capsid protein coats (PC) that encapsulate the virus genome, and virus-like particles (VLPs), a capsid without the viral genome.

Mini Review Open Access

Cancer-Related Pain: Inside a New Dynamic Personalized Approach. A Narrative Review

Mariateresa Giglio, Giustino Varrassi, Filomena Puntillo

Chronic cancer-related pain, according to the latest International Classification of Diseases (ICD-11), is defined as “chronic pain caused by the primary cancer itself or metastases (chronic cancer pain) or its treatment (chronic post-cancer treatment pain)”.

Short Communication Open Access

MEK Inhibition in KRAS Mutated NSCLC: Quo vadis?

Kira-Lee Koster, Patrizia Froesch, Michael Mark, Sacha I. Rothschild, Martin Früh

Lung cancer continues to be the leading cause of cancer deaths worldwide. Approximately 85% of lung cancers are histologically classified as non-small cell lung cancer (NSCLC) of which adenocarcinoma is the most frequent subtype.

Review Article Open Access

Clinical, FDG-PET and Molecular Markers of Immune Checkpoint Inhibitor Response in Patients with Advanced Merkel Cell Carcinoma

Julia R Dixon-Douglas, Luke S McLean, Alex Caneborg, Richard W Tothill, Grace Kong, Rodney J Hicks, Shahneen Sandhu

Merkel cell carcinoma (MCC) is a rare, highly aggressive, neuroendocrine cancer of the skin with an increasing incidence. MCC occurs predominantly in older adults with risk factors including high exposure to ultra-violet (UV) light and immunosuppression.

Research Article Open Access

Immunophenotypic Characterization by Flow Cytometry of Chronic Lymphoid Leukemia

Yenisey Triana Marrero, Vianed Marsán Suárez, Yaneisy Duarte Pérez, Gabriela Díaz Domínguez, Imilla Casado Hernández, Elizabeth Hernández Ramos, Rosa María Lam Díaz, Consuelo Milagros Macías Abraham

Chronic lymphoid leukemia (CLL) is a malignant hematological disease characterized by the accumulation of mature lymphocytes with a defect in the induction of apoptosis that massively accumulate in peripheral blood (PB), bone marrow (BM) and lymphoid tissues.

Research Article Open Access

Biomarkers of Pembrolizumab Efficacy in First-Line Advanced PD-L1 ≥ 50% Non-Small Cell Lung Cancer Treatment

Luis Cabezón-Gutiérrez, Sara Custodio-Cabello, Magda Palka-Kotlowska, Silvia María Sanchez-Luis, Parham Khosravi-Shahi

Lung cancer is the leading cause of cancer death worldwide. In 2020, a total of 19 million cancer patients were diagnosed, of which 11.4% were lung cancer, causing 18% of all cancer deaths. In 2020 in Spain, 29,638 cases were estimated.

Commentary Open Access

Humanized Chimeric Antigen Receptor (CAR) T cells

Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Roddy S. O’Connor

In 1989, researchers proposed an intricate strategy in the field of adoptive cell therapy (ACT). Using the T-cell receptor (TCR) as a template, they replaced the coding sequence for the Vα and Vβ chains with the antigen- recognition domains from an antibody (VH and VL chains).

Short Communication Open Access

Therapeutic Monoclonal Antibodies: Future Prospectives

Lobna Abdel Aziz Kilany, Mohammad Mabrouk Aboulwafa, Hamdallah Hafez Zedan

Therapeutic monoclonal antibodies (mAb) have the potential to treat a wide range of various diseases and disorders including cancer, chronic autoimmune and inflammatory diseases, allergies, infections, transplantations, and cardiovascular diseases.

Research Article Open Access

High Expression of TIM ₃ and Galectin ₉ on Immunohistochemistry Staining of Tumor Specimen at Diagnosis in Pediatric Patients with Ewing Sarcoma

Stephanie J. Si, Gerald B. Wertheim, David M. Barrett

The concept of immunotherapy has been traced as far back to third century BC Qin dynasty in China through the purposeful inoculation of Variola minor to prevent smallpox. 

Short Communication Open Access

Polycyclic Aromatic Hydrocarbons and Mammary Cancer Risk: Does Obesity Matter too?

Lydia Lichtiger, Janelle Rivera, Debashish Sahay, Rachel L. Miller

Breast cancer is the most commonly diagnosed cancer in women in the United States. Breast cancer incidence rates, particularly among younger women, have been increasing since the 1930s, and are only partially explained by changes in parity, age at first birth, and improved screening and detection. Many questions remain unanswered regarding the mechanisms that underlie current risk.

Commentary Open Access

Anti-PD₁ Therapy in Lynch Syndrome-associated Recurrent Glioblastoma

Wendy J Sherman

When a patient is diagnosed with a glioblastoma, they are often blindsided with the diagnosis, experiencing symptoms typically developing over only days to weeks and then often undergoing a craniotomy within days of presentation, only to then be given a terminal diagnosis.

Commentary Open Access

Profiling the Energy Metabolism at the Cell Subpopulation Level

Karim Benihoud, Catherine Brenner

Although being a complex pathology with genetic as well as non-genetic etiologies, cancer is characterized by a limited series of hallmarks including energetic metabolism reprogramming.

Short Communication Open Access

Quantifying Neural Stem Cell-Derived Extracellular Vesicle Uptake Using Imaging Flow Cytometry

Taylor J. Elliso, Brian J. Jurgielewicz, Steven L. Stice, Yao Yao

Nanomedicine, which includes nanoparticles and other nanomaterials for diagnosis and therapeutic delivery to treat numerous diseases, is making advances. 

Review Article Open Access

Dose-dependent Effects of Vitamin C on Cancer Regulation: A Review

Faheem Hadi, Tahir Maqbool, Saira Aftab, Muhammad Tahir, Shazia Ramzan, Komal Kiran, Arif Malik, Shabana Akhtar

Vitamin C, also known as ascorbate or ascorbic acid, is an essential water-soluble vitamin required for several physiological mechanisms in plant and animal cells.

Review Article Open Access

Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma

Aakash Patel, Daniel I. Bisn, Hiren V. Patel, Saum Ghodoussipour, Biren Saraiya, Tina Mayer, Eric A. Singer

Bladder cancer is one of the most common and expensive cancers in the United States, with an expected 81,400 new cases and 17,980 deaths in 2020 alone. The incidence is increased among white men and diagnoses often occur in the 7th decade of life.

Commentary Open Access

Relevance of Neuropilin ₁ and Neuropilin ₂ Targeting for Cancer Treatment

Aurore Dumond, Gilles Pagès

Neuropilins (NRPs) are a class of transmembrane glycoprotein co-receptors including Neuropilin 1 (NRP1) and Neuropilin 2 (NRP2). They are the co-receptors of different families of receptors, thus they are involved in many hallmarks of cancer.

Commentary Open Access

Emerging Roles of Pseudogene RNAs in Antitumor and Antiviral Immunity

Yoo Jane Han, Michaela U. Gack, Olufunmilayo I. Olopade

Tumor immunity and immunotherapy have become increasingly important in treatment strategies for a variety of malignancies including advanced triple negative breast cancer.

Commentary Open Access

Exosomes, PD-L₁ and aGvHD: Perspectives for WJMSCmediated Therapy

Meizhang Li, Haitham Abdelhakim, Mitchell W. Braun, Andrew K. Godwin

Tumor-derived small extracellular vesicles or exosomes which carry the checkpoint PD-L1 are directly involved in immune evasion and uncontrolled tumor growth. We have recently reported that PD-L1 is also enriched on Wharton’s Jelly Mesenchymal Stromal Cell (WJMSC)-associated exosomes.

Commentary Open Access

Cervical Cancer Prevalence in sub-Saharan Africa and HPV Vaccination Policy: A Public Health Grand Challenge?

Eric Asempah

“Women are not dying because of diseases we cannot treat. They are dying because societies have yet to make the decision that their lives are worth saving.”

Commentary Open Access

Hepatocellular Carcinoma: Diagnosis, Therapy and Molecular Investigations

Veronica Bazzani, Riccardo Pravisani, Umberto Baccarani, Carlo Vascotto

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and, with rapidly increasing incidence in the last two decades, constitutes a major global health problem.

Review Article Open Access

Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy

Gourab Gupta, Kristina Borglum, Hexin Chen

Cell Death has long been considered to be an inevitable part of the life cycle of a cell and hence, considered a familiar consequence of cellular life.

Commentary Open Access

Lenalidomide Maintenance After Autologous Stem Cell Transplant: The Utility of Real-World Data and Future Areas of Study

Hannah M Cherniawsky, Christopher P Venner, Esther Masih-Khan, Donna Reece

Low-dose, lenalidomide maintenance following autologous stem cell transplantation (ASCT) is the current standard of care in patients with newly diagnosed multiple myeloma (NDMM) based on results from large, randomized controlled trials and a meta-analysis which demonstrated improved overall (OS) and progressionfree survival (PFS).

Commentary Open Access

Expanding the Cancer Neoantigen Peptide Repertoire beyond In silico Tools

Amit Jain, Jackwee Lim

CD8+ cytotoxic T cells recognise and kill cancer cells that present immunogenic peptides bound to the cell surface major histocompatibility complex class I (MHC-I) molecules.

Review Article Open Access

SHP₂ Inhibition as a Promising Anti-cancer Therapy: Function in Tumor Cell Signaling and Immune Modulation

Jiawan Wang, Lindy Zhang, Christine A. Pratilas, Nicolas J. Llosa

The SHP2 phosphatase consists of one protein tyrosine phosphatase catalytic domain (PTP domain), two tandem Src homology 2 (SH2) domains (N-SH2 and C-SH2), and a C-terminal tail with two tyrosine phosphorylation sites (Tyr542 and Tyr580)

Commentary Open Access

Small-molecule Interferon Inducers for Cancer Immunotherapy Targeting Non-T cell-inflamed Tumors

Eunha Kim, Sanghee Lee

Since the discovery of escaping mechanism of tumor from negative immune regulation, the paradigm of drug discovery for anti-cancer agents has been dramatically shifted to cancer immunotherapy (e.g., dendritic cell therapy, CAR-T cell therapy, or antibody therapy) by stimulating patient’s immune system to treat cancer. 

Commentary Open Access

Long Non-coding RNAs in the Pathophysiology of Multiple Myeloma New Insights on the Role of CRNDE

Simone Zocchi, Antoine David, Michele Goodhardt, David Garrick

Over the past 15 years, long non-coding RNAs (lncRNA) have emerged as an important class of regulatory molecules. The currently accepted definition is that lncRNA refers to RNA molecules with little or no protein-coding potential, and which are greater than 200 nucleotides in length, a size cut-off chosen largely to distinguish them from the more-extensively characterised group of small non-coding regulatory RNAs, which includes micro (mi)RNAs, small inhibitory (si)RNAs and PIWI-interacting (pi)RNAs.

Commentary Open Access

TFAP-2: A Special Regulator with Bidirectional Effect in Human Cancer

Li-Nan Wang, Yi-Liu Yang, Lin-Yong Zhao

Abnormality of transcription factors’ activity has been found in signal pathways of many cancers. The AP-2 family of transcription factors (TFAP2) is one of the most representative families with this characteristic.

Commentary Open Access

SPANX Regulation of LAMIN A/C Network: Perspectives in Cancer and Laminopathies

Ikrame Lazar, Bertrand Fabre

Cancer/testis antigens (CTA) are tumor antigens whose expression is normally restricted to the testis. More than half of CTA genes are located on the X chromosome and form a branch called X-CTA [1]. Unlike the remaining CTA genes located throughout the genome, multigene X-CTA families are present as clusters on the X chromosome.

Review Article Open Access

Immunotherapy in Pediatric Acute Lymphoblastic Leukemia

Julie M. Asare, Cara A. Rabik, Stacy Cooper, Patrick A. Brown

Leukemia is the most common childhood malignancy and is the most common cause of cancer death before the age of 20. Pediatric leukemia can be subdivided into acute versus chronic and lymphoid versus myeloid leukemia.

Commentary Open Access

Susceptibility of Malignant Brain Tumors to 5-aminolaevulinic Acid Mediated Photodynamic Therapy: Direct Phototoxicity and Immunological Effects

Angeliki Datsi, Rüdiger V. Sorg

Recently we published the article ‘Accumulation of protoporphyrin IX in medulloblastoma cell lines and sensitivity to subsequent photodynamic treatment’.

Commentary Open Access

High Lymph Node Positive to Sampled Ratio as a Potential Indication for Postoperative Radiation Therapy in Patients with pN₂ Non-small-cell Lung Cancer

Nikhil P. Mankuzhy, Muayad F. Almahariq, Craig W. Stevens, Thomas J. Quinn

Despite advances in cancer treatment and screening, lung cancer remains the leading cause of cancer death in the United States. The majority of cases are locally advanced non-small cell lung cancer (NSCLC), treatment of which usually includes a bi- or tri-modality therapy utilizing a combination of surgery, chemotherapy, and radiation therapy.

Review Article Open Access

Emerging Strategies to Attack Polyploid Cancer Cells

Jing Zhang, Shenqiu Zhang, Qiong Shi, Dun Yang, Thaddeus D. Allen

While cells with a 2n complement of chromosomes are defined as diploid, cells that possess greater than 2n are referred to as polyploid.

Commentary Open Access

Management of Appendiceal Neuroendocrine Tumors: Beyond Tumor Size

Jace P. Landry, Yvette B. Mattison, Robert A. Ramirez, J. Philip Boudreaux, Eugene A. Woltering, Mary A. Maluccio, Ramcharan Thiagarajan

In 1987, Charles Moertel and colleagues published a landmark series on 150 patients with appendiceal neuroendocrine tumors (ANET) that showed patients with tumors less than 2 cm in size had no evidence of regional or distant metastasis.

Review Article Open Access

Ovarian Function Suppression Plus Aromatase Inhibitors or Tamoxifen in Premenopausal HR-positive Breast Cancer

Xueqing Xie, Yiqun Yao, Dianlong Zhang

Breast cancer is the most common type of malignant tumor in women, accounting for 30% of women’s cancer, while the mortality rate ranks second among women’s cancer. Twenty-five percent of all breast cancer patients are premenopausal patients, and 7% of patients are younger than 40 years old.

Review Article Open Access

Mitochondria Autoimmunity and MNRR₁ in Breast Carcinogenesis: A Review

Félix Fernández Madrid, Lawrence I. Grossman, Siddhesh Aras

Recently, Aras et al. reported that MNRR1, a nuclear DNA (nDNA)-encoded mitochondrial antigen, promotes cancer cell migration and the development of metastasis as a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis.

Short Communication Open Access

Hepatocellular Carcinoma: Animal Models Available to Characterize Tumor Immunology and Optimize Treatment Development

Gael S Roth, Zuzana Macek Jilkova, Thomas Decaens

Hepatocellular carcinoma (HCC) is the second cause of cancer-related death worldwide with almost 1 million new cases per year. At the diagnosis, 70% of patients have only access to a palliative treatment with few therapeutic options mostly represented by tyrosine kinase inhibitors such as sorafenib and lenvatinib in first line; regorafenib and cabozantinib in second line.

Commentary Open Access

Prevention of Lung Cancer Growth by Water Extract from Euglena gracilis

Susumu Ishiguro, Jeffrey Comer, Masaaki Tamura

As a source of novel drugs and dietary supplements, natural products from plants and animals have been studied for more than decades. Unicellular algae, such as Chlorella, Spirulina and Euglena, are such resources. Euglena gracilis is a unicellular green alga found in fresh water.

Review Article Open Access

Immunological Features with DNA Microsatellite Alterations in Patients with Colorectal Cancer

Maide Ö. Raeker, John M. Carethers

DNA microsatellites are tandemly repeating short (1-6 base pairs) DNA motifs, such as mononucleotide (A)n, dinucleotide (CA)n, trinucleotide (CAG)n, and tetranucleotide (AAAG)n, with each motif potentially repeating up to 50 times.

Review Article Open Access

The Role of ERO1α in Modulating Cancer Progression and Immune Escape

Brennan D. Johnson, Werner J. Geldenhuys, Lori A. Hazlehurst

The failure to eradicate minimal residual disease often located at metastatic sites and/or the bone marrow niche continues to be a clinical barrier for successful treatments in cancer.

Review Article Open Access

Progress in Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Cardiotoxicity

Feng Wang, Shukui Qin

Immune checkpoint inhibitors (ICIs) are a new type of broad-spectrum antitumor drugs, which mainly include cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) and its ligand PD-L1 inhibitors. Since 2011, ICIs have been approved for more than 20 kinds of malignant tumors.

Review Article Open Access

Methylation Status of Tumor Suppressor Genes in Circulating DNA of PDAC Patients: Facts and Hopes

Bharti Garg, Nidhi Singh, Anoop Saraya

Pancreatic cancer is one of the most lethal solid tumor malignancies and it is projected to become a leading cause of cancer related deaths in coming years. It is often diagnosed at an advanced stage owing to the lack of specific symptoms and rapid invasion.

Commentary Open Access

Inhibition of Autophagy and Immune Response: Alpha-fetoprotein Stimulates Initiation of Liver Cancer

Mingyue Zhu, Mengsen Li

Alpha-fetoprotein (AFP) is a tumorous marker for the diagnosis of hepatocellular carcinoma (HCC), it is synthesized mainly by the embryo yolk sac, fetal liver and the gastrointestinal tract. AFP belongs to the family of protein products of albuminoid genes, which are located in tandem arrangement in chromosome 4 (region 4q11-q13).

Commentary Open Access

Inference of Clonal Copy Number Alterations from RNASequencing Data

Akdes Serin Harmanci, Arif O. Harmanci, Xiaobo Zhou

Tissues are composed of various types of interacting cells [1]. To understand the cellular organization and function in tissues, it is necessary to identify all of the different cell types and the locations of these different cell types within tissue structures.

Commentary Open Access

Purinergic System and Cervical Cancer: Perspectives

Marta Schmidt Pfaffenzeller, Maria Luiza Mukai Franciosi, Adriana Fuganti Wagner, Andreia Machado Cardoso

We have recently published an article entitled “Purinergic signaling and tumor microenvironment in cervical Cancer”. In this paper, we reviewed the last studies about purinergic signaling and cervical cancer, highlighting the intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine - components of the purinergic system.

Editorial Open Access

Cellular Response to Stress: At the Crossroads between Immunosenescence and Cancer

Christian R. Gomez

Aging is a complicated process not yet fully understood. Driven by a variety of stressors such as infectious agents, radiation, intracellular stress, and stressing metabolic conditions, molecular damage occurs over time. Among many consequences, age-related unchecked molecular damage leads to immunosenescence, a hallmark of aging.

Research Article Open Access

Involvement of D-Loop Mutations in the Occurrence of Ovarian Carcinoma

Oumar Mane, Fatimata Mbaye, Mbacké Sembene

Each cell in the body contains hundreds of mitochondria; each mitochondrion contains several DNA molecules, each carrying 37 genes that participate in the production of energy.

Commentary Open Access

Verrucous Carcinoma of the Esophagus: Its Unique Etiology and Association with Human Papilloma Virus

Satoshi Tabuchi, Kazuo Koyanagi, Soji Ozawa, Shigeyuki Kawachi

Verrucous carcinoma is an extremely rare disease, and it is unique in terms of its appearance, growth pattern, and etiology. In 1948, Ackerman first described verrucous squamous cell carcinoma (VSC) as a variant of oral squamous cell carcinoma, and he collected 31 cases of oral neoplasms under the name, “Verrucous Carcinoma of the Oral Cavity.”

Commentary Open Access

Protein Therapeutics from Monolayer to Spheroids- A Model for Preclinical Investigations

Neha Arora, Siddhartha Sankar Ghosh

The arrival of recombinant insulin in the pharmaceutical market paved a new direction for the clinical potential of proteins. Thus, the pharmaceutical industry underwent a paradigm shift towards proteins as therapeutic moieties.

Commentary Open Access

Aerosol Distribution Pattern of a Single-port Device: New Perspective Treatment for Peritoneal Carcinomatosis in Brazil

Rafael Seitenfus, Lívia Brancher Gravina, Gustavo Andreazza Laporte

The local and peritoneal recurrence play a vital role in the natural history of the evolution of gastrointestinal and ovarian neoplasms. Different methods of applying intraperitoneal chemotherapy were used perioperatively to consolidate or control peritoneal carcinomatosis.

Editorial Open Access

Artificial Intelligence and Machine Learning in Cancer Care: Current Applications and Future Perspectives

Sachin Kumar Deshmukh

Cancer is the second most common cause of death worldwide, accounting for an estimated 9.6 million deaths in the year 2018, a number that is expected to grow to more than 13 million by 2030. In the past decade, we have witnessed unprecedented scientific advancement in the understanding of cancer etiology, prevention, diagnosis and development of new therapeutic strategies.

Review Article Open Access

Relationship of lncRNA to Breast Cancer

Alpizar-Reyes B, Barrera-Tamariz MR, Contreras-Gómora I, Munguia-Arriaga MA, Ávila-Avilés RD

At present, breast cancer is more frequently diagnosed in women than in men. According to global cancer statistics, each year more than 1,675,000 women are diagnosed and more than 500,000 of them die. Some subtypes of breast cancer have been described.

Short Communication Open Access

Combination Therapies with Anti-angiogenesis and B₇-H₃ Blockade in Cancers

Ruoqin Wang, Tongguo Shi, Weichang Chen

Tumor angiogenesis, a hallmark of cancer, is a critical step in the tumorigenesis of solid cancers. The process of tumor angiogenesis is orchestrated by a range of secreted factors, signaling pathways as well as nonendothelial cells.

Commentary Open Access

Autophagy: When to strike?

Shadi Zahedi, Jean M. Mulcahy Levy

Autophagy was originally viewed as a widely conserved multistep lysosomal degradation pathway in eukaryotes. It includes the formation of autophagosomes, doublemembrane structures engulfing cytoplasm with damaged organelles during the degradation process.

Editorial Open Access

CTLA-4 and PD-L₁ or PD_-1 Pathways: Immune Checkpoint Inhibitors and Cancer Immunotherapy

Sachin Kumar Deshmukh

The immune system developed certain checks and balance to control or inhibit the reactivity against normal cells of the body. Uncontrolled immune responses to the non-self entities such as bacteria, viruses, parasites, or mutated self-antigens can cause an inflammatory reaction and autoimmune diseases.

Review Article Open Access

Leucocyte-Tumor Cell Hybridization Can Initiate Cancer Metastasis

John M. Pawelek, Zachary Grasmick, Eric Duvall, Greggory S. LaBerge

According to estimates from the International Agency for Research on Cancer, by the year 2030 there will be 22 million new cancer cases and 13 million deaths per year. The main reason for death from cancer is not the initial tumor but it’s metastasis to distant parts of the body, yet this process has remained poorly understood for quite some time.

Commentary Open Access

Commentary on "The Gene Master Regulators GMR Approach Provides Legitimate Targets for Personalized, Time-Sensitive Cancer Gene Therapy"

Dumitru Andrei Iacobas

For decades, the scientific community tried hard to identify the gene biomarkers whose mutations or regulations cause (better say are associated with) specific forms of cancer. For instance, the September 17th 2019 release of the Genomic Data Commons Data Portal includes 3,142,246 mutations detected in 22,872 genes sequenced from 37,075 cases of cancers localized in 67 primary sites.

Review Article Open Access

Salivary Protein Antigens for Breast Cancer Biomarkers

Imad Abrao Nemeir, Joseph Saab, Walid Hleihel, Abdelhamid Errachid, Nadia Zine

Breast Cancer is the most regularly diagnosed type of cancer in women in the world, making up on its own 25% of all cases, or nearly 2 million new cases in 2018, and 15% of all cancer related deaths, or around 626,700 deaths for that same year.

Review Article Open Access

pMB FLASH - Status and Perspectives of Combining Proton Minibeam with FLASH Radiotherapy

Judith Reindl, Stefanie Girst

Proton minibeam radiotherapy (pMBRT) is an external beam radiotherapy method with reduced side effects by taking advantage of spatial fractionation in the normal tissue. Due to scattering, the delivered small beams widen in the tissue ensuring a homogeneous dose distribution in the tumor. In this review, the physical and biological principles regarding dose distribution and healing effects are explained. In the last decade, several preclinical studies have been conducted addressing normal tissue sparing and tumor control in-vitro and in-vivo, using human skin tissue and mouse or rat models. The major results acquired in these studies are summarized. A further newly emerging therapy method is FLASH radiotherapy, i.e. the treatment using ultra-high dose rates. The possibility of combining these methods in proton minibeam FLASH therapy (pMB FLASH) is worked out. Additionally, technical feasibility and limitations will be discussed by looking at simulations as well as preclinical studies and also pointing out new ways of delivering the desired tumor dose, such as interlacing. We will also highlight the opportunities that emerge regarding high dose radiation, hypofractionation and the combination with immunotherapy.

Editorial Open Access

Chimeric Antigen Receptor CAR NK Cells Emerging Immunotherapy for the Treatment of Cancer

Sachin Kumar Deshmukh

Although NK cells are recognized as effector lymphocytes of the innate immune system, they also regulate the adaptive immune response by releasing inflammatory cytokines and developing immunological memory. Unlike other lymphocytes such as T or B cells, NK cells do not express rearrangeable, antigen-specific receptors. 

Research Article Open Access

Prevalence of Symptom Clusters in Cancer Patients at First Presentation in Palliative Care Clinic as per Different Disease Groups

Irum Ghafoor, Haroon Hafeez, Farhat Naz, Muhammad Abubakar, Arif Jamshed

Cancer has its own disease burden and patients usually suffer from symptom clusters when they are referred for palliative treatment. Identification of symptom cluster trajectories will help clinician to take into account measures that can optimize quality of life of palliative patients. Therefore the aim of this paper is to determine the overall prevalence of symptoms and symptoms clusters in different disease groups according to etiology at the time of first visit to Palliative care clinic by using HIS Palliative First Assessment note indicating Edmonton symptom scale.