MHC heterogeneity and response of metastases to immunotherapy

In recent years, immunotherapy has proven to be an effective treatment against cancer. Cytotoxic T lymphocytes perform an important role in this anti-tumor immune response, recognizing cancer cells as foreign, through the presentation of tumor antigens by MHC class I molecules. However, tumors and m...

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Bibliographic Details
Published in:Cancer and metastasis reviews 2021-06, Vol.40 (2), p.501-517
Main Authors: Algarra, Ignacio, Garrido, Federico, Garcia-Lora, Angel M.
Format: Article
Language:English
Subjects:
Analysis
Antigen (tumor-associated)
Antigen presentation
B cells
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Care and treatment
Cytotoxicity
Development and progression
Histocompatibility antigen HLA
Immune response
Immunosuppression
Immunosurveillance
Immunotherapy
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Metastases
Metastasis
Molecular modelling
Oncology
Phenotypes
Precision medicine
T cells
Tumor antigens
Tumor cells
Tumors
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Summary:In recent years, immunotherapy has proven to be an effective treatment against cancer. Cytotoxic T lymphocytes perform an important role in this anti-tumor immune response, recognizing cancer cells as foreign, through the presentation of tumor antigens by MHC class I molecules. However, tumors and metastases develop escape mechanisms for evading this immunosurveillance and may lose the expression of these polymorphic molecules to become invisible to cytotoxic T lymphocytes. In other situations, they may maintain MHC class I expression and promote immunosuppression of cytotoxic T lymphocytes. Therefore, the analysis of the expression of MHC class I molecules in tumors and metastases is important to elucidate these escape mechanisms. Moreover, it is necessary to determine the molecular mechanisms involved in these alterations to reverse them and recover the expression of MHC class I molecules on tumor cells. This review discusses the role and regulation of MHC class I expression in tumor progression. We focus on altered MHC class I phenotypes present in tumors and metastases, as well as the molecular mechanisms responsible for MHC-I alterations, emphasizing the mechanisms of recovery of the MHC class I molecules expression on cancer cells. The individualized study of the HLA class I phenotype of the tumor and the metastases of each patient will allow choosing the most appropriate immunotherapy treatment based on a personalized medicine.
ISSN:0167-7659
1573-7233
DOI:10.1007/s10555-021-09964-4