Regulation of the antigen presentation machinery in cancer and its implication for immune surveillance

Balasubramanian, A; John, T; Asselin-Labat, ML

Author(s): Balasubramanian, A; John, T; Asselin-Labat, ML;
Details: Publication Year 2022-04-29,Volume 50,Issue #2,Page 825-837
Journal Title: Biochemical Society Transactions
Publication Type: Review
Abstract: Evading immune destruction is one of the hallmarks of cancer. A key mechanism of immune evasion deployed by tumour cells is to reduce neoantigen presentation through down-regulation of the antigen presentation machinery. MHC-I and MHC-II proteins are key components of the antigen presentation machinery responsible for neoantigen presentation to CD8+ and CD4+ T lymphocytes, respectively. Their expression in tumour cells is modulated by a complex interplay of genomic, transcriptomic and post translational factors involving multiple intracellular antigen processing pathways. Ongoing research investigates mechanisms invoked by cancer cells to abrogate MHC-I expression and attenuate anti-tumour CD8+ cytotoxic T cell response. The discovery of MHC-II on tumour cells has been less characterized. However, this finding has triggered further interest in utilising tumour-specific MHC-II to harness sustained anti-tumour immunity through the activation of CD4+ T helper cells. Tumour-specific expression of MHC-I and MHC-II has been associated with improved patient survival in most clinical studies. Thus, their reactivation represents an attractive way to unleash anti-tumour immunity. This review provides a comprehensive overview of physiologically conserved or novel mechanisms utilised by tumour cells to reduce MHC-I or MHC-II expression. It outlines current approaches employed at the preclinical and clinical trial interface towards reversing these processes in order to improve response to immunotherapy and survival outcomes for patients with cancer.
Keywords: *Antigen Presentation; CD4-Positive T-Lymphocytes; Humans; Immunologic Surveillance; Immunotherapy; *Neoplasms; cancer; immune response; major histocompatibility complex
Department(s): Medical Oncology
PubMed ID: 35343573
Publisher's Version: https://doi.org/10.1042/BST20210961
Open Access at Publisher's Site: https://doi.org/10.1042/bst20210961
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-26 05:45:23

Last Modified: 2024-09-26 05:48:04