Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity

The HLA-I molecules help our immune system fight off diseases and cancer by recognizing specific peptides. Some HLA-I variants can bind a wide variety of peptides, which could be helpful against viruses but its implications on cancer immune response are unknown. Our study found that cancer patients with HLA-I variants that bind many different peptides have worse survival when treated with immune checkpoint blockade immunotherapy. This seems to be because their immune system has trouble differentiating between cancer proteins and normal body proteins, making it more likely to ignore cancer cells. In essence, the ability of HLA-I variants to bind many peptides may compromise the fight against cancer while possibly offering protection against viruses.