HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events

As molecules responsible for presenting antigens to T lymphocytes, leukocytes antigens (HLAs) play a vital role in cancer immunology. This review aims to provide current understanding of HLAs in tumour immunology.

Perspectives on how HLA alterations may contribute to the immune escape of cancer cells and resistance to immunotherapy, and potential methods to overcome HLA defects were summarized. In addition, we discussed the potential association between HLA and immune-related adverse events (irAEs), which has not been reviewed elsewhere.

Downregulation, loss of heterogeneity and entire loss of HLAs are responsible for the immune escape of tumour cells. The strategies to overcome the HLA defects can be effective therapies of cancer. Compared with classical HLA-I, non-classical HLA-I molecules, such as HLA-E and HLA-G, appear to be more reliable predictors of prognosis, as they tend to play immunosuppressive roles in antitumor response. Relative diversified or high expression of classical HLA-I are potential predictors of favourable response of immunotherapy. Certain HLA types may be associated to enhanced affinity to self-antigen-mimicked tumour-antigens, thus may positively correlated to irAEs triggered by checkpoint inhibitors.

Further studies exploring the relationship between HLAs and cancer may not only lead to the development of novel therapies but also bring about better management of irAEs.