How HLA influences response to immunotherapy (Part 1)

Effective CD8+ T cell-dependent elimination of cancer cells relies upon the presentation of tumor antigens on human leukocyte antigen (HLA) class I molecules. Yet, the extent to which patient-specific HLA class I genotype influences response to anti-PD-1 or anti-CTLA-4 immunotherapy remains unknown. To address this issue, we determined the HLA class I genotype of advanced cancer patients treated with immune checkpoint blockade (ICB). We show that maximal heterozygosity at HLA class I loci (A, B, and C) conferred an advantage on overall survival after ICB compared to patients who were homozygous for at least one locus. We also found that the HLA-B44 supertype was consistently associated with prolonged survival in patients with melanoma treated with ICB.