HLA class I antigen processing machinery defects in antitumor immunity and immunotherapy

Abstract

Human leukocyte antigen (HLA) class I antigen-processing machinery (APM) plays a crucial role in the synthesis and expression of HLA class I tumor antigen-derived peptide complexes; the latter mediate the recognition and elimination of malignant cells by cognate T cells. Defects in HLA class I APM component expression and/or function are frequently found in cancer cells, providing them with an immune escape mechanism that has relevance in the clinical course of the disease and in the response to T-cell-based immunotherapy. The majority of HLA class I APM defects (>75%) are caused by epigenetic mechanisms or dysregulated signaling and therefore can be corrected by strategies that counteract the underlying mechanisms. Their application in oncology is likely to improve responses to T-cell-based immunotherapies, including checkpoint inhibition.

Keywords: HLA class I; T cell recognition; antigen-processing machinery; epigenetics; immune escape; immunosurveillance.