Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy

TLDR

HLA genotype influences cancer immunotherapy response by determining how CD8⁺ T cells recognize tumor peptides presented by the three major HLA‑I genes, affecting immune activation and vaccine design. The study investigates whether germline HLA‑I genotype affects T‑cell recognition of tumor peptides and the response to checkpoint inhibitor immunotherapy. In a cohort of over 1,500 patients, HLA‑I heterozygosity was linked to improved survival compared to homozygosity at one or more loci. Reference: Chowell et al., *Science*, this issue p.

Abstract

HLA genotype affects response Immunotherapy works by activating the patient's own immune system to fight cancer. For effective tumor killing, CD8 + T cells recognize tumor peptides presented by human leukocyte antigen class I (HLA-I) molecules. In humans, there are three major HLA-I genes ( HLA-A, HLA-B , and HLA-C ). Chowell et al. asked whether germline HLA-I genotype influences how T cells recognize tumor peptides and respond to checkpoint inhibitor immunotherapies (see the Perspective by Kvistborg and Yewdell). They examined more than 1500 patients and found that heterozygosity at HLA-I loci was associated with better survival than homozygosity for one or more HLA-I genes. Thus, specific HLA-I mutations could have implications for immune recognition and for the design of epitopes for cancer vaccines and immunotherapies. Science , this issue p. 582 ; see also p. 516