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Cancer immunotherapy, including immune checkpoint inhibitors, adoptive cell therapies and tumor vaccines, has recently shown impressive results in the treatment of multiple cancers. The key step shared by these therapies requires T cells to recognize the specific peptides presented by the human leukocyte antigens (HLAs) on the membranes of tumor cells and subsequently kick off an immune response. HLA class I molecules exist in most human cell types and can interact with T cell receptors (TCRs) to activate T cells, which are important molecules that induce adaptive immune responses. In recent years, research on cell therapy has mainly focused on CD8 T cell therapy, such as tumor-infiltrating lymphocytes (TILs) therapy and TCR-engineered T cells (TCR-Ts) therapy, which are both HLA-dependent immunotherapy. However, tumor cells may escape T cell attack through HLA downregulation, which limits HLA-dependent immunotherapy to some extent. Thus, HLA-independent immune cell therapies such as chimeric antigen receptor T-cell therapy, natural killer cell therapy and CD4 T cell therapy shed new light on this issue. In this review, we summarized the mechanisms of antigen presentation by HLAs, the latest progress of HLA-presented peptides identification, and the current status of HLA-dependent and -independent adoptive immunotherapies.

Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies