Review Article Open Access
Volume 3 | Issue 1 | DOI: https://doi.org/10.33696/Signaling.3.065

Interferon Gamma, MHC Class I Regulation and Immunotherapy

  • 1International Centre for Cancer Vaccine Science, University of Gdansk, ul. Kladki 24, 80-822 Gdansk, Poland
  • 2Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland EH4 2XR, UK
  • #These authors contributed equally to this work
+ Affiliations - Affiliations

Corresponding Author

Maria Gómez-Herranz, maria.gomez@ug.edu.pl
Sachin Kote, sachin.kote@ug.edu.pl 

Received Date: November 30, 2021

Accepted Date: January 21, 2022


The activation of endogenous IFNγ signaling pathway or the administration of recombinant IFNγ increases the expression of MHC-I. MHC-I molecules are core elements for antigen recognition in tumor cells. A better understanding of the regulation of their expression would contribute to counteracting tumor immune escape and enduring permanent tumor rejection. Efficient and functional expression of HLAs dramatically impacts the number of tumor-associated antigens presented to CTL for cell recognition. Many patients diagnosed with various types of cancer have inhibited the IFNγ signaling pathway. This review explores how anomalies associated with IFNγ signaling in tumor cells affect HLA-I expression, current immunotherapies association, and outcome. Globally, MHC-I lesions could be divided into reversible and permanent. Irreversible lesions cannot be recapitulated; hence, the patient will not respond to immunotherapies requiring MHC-I activity. However, gaining precise and systematic molecular knowledge improves tumor stratification, which could help predict which tumors will recover expression of MHC-I. Complementary IFNγ effectors can function as a compensatory mechanism that restores the expression of HLA-I proteins in tumors with deleterious IFNγ pathways. For those non-responsive patients with inactive IFNγ pathways, designing personalized approaches to recover HLA-I expression can make the tumor sensitive to immunotherapy, leading to a better outcome.


MHC class I, HLA, IFNγ, Immunotherapy

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