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.

During the last few decades, immunotherapy is considered to be an important approach to help our immune system to fight various kinds of diseases, such as tumor. Sometimes, it works very well for some types of cancers, for example: bladder cancer, colorectal cancer, breast cancer and lymphoma.

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.

Cancer nanomedicine was originally developed for more efficient delivery of chemotherapeutic agents into tumor, and has been extensively employed as a therapeutic for cancer treatment owing to its unique features in drug delivery, diagnosis and imaging, as well as the therapeutic nature of some nanomaterials themselves.

Cells of the innate and adaptive arm of the immune system including macrophages, natural killer (NK) cells, neutrophils, T cells, and B cells, etc. are crucial for the maintenance of the body’s homeostatic balance and prevention of multiple diseases including cancer.