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

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Science  02 Feb 2018:
Vol. 359, Issue 6375, pp. 582-587
DOI: 10.1126/science.aao4572

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