Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation

Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers t...

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Bibliographic Details
Published in:Frontiers in immunology 2021-03, Vol.12, p.636568
Main Authors: Dhatchinamoorthy, Karthik, Colbert, Jeff D, Rock, Kenneth L
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
cancer immune evasion
Gene Deletion
Gene Expression Regulation, Neoplastic
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class I - immunology
Histocompatibility Antigens Class I - metabolism
Humans
Immunology
interferon
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - metabolism
MHC I antigen presentation
Mutation
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Signal Transduction
TAP1
Tapasin
Transcription, Genetic
Tumor Escape
Tumor Microenvironment
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Summary:Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers that are expressing mutated proteins. In order for many cancers to arise and progress, they need to evolve mechanisms to avoid elimination by CD8 T cells. MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Here we review the evidence that loss of MHC I antigen presentation is a frequent occurrence in many cancers. We discuss new insights into some common underlying mechanisms through which some cancers inactivate the MHC I pathway and consider some possible strategies to overcome this limitation in ways that could restore immune control of tumors and improve immunotherapy.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.636568