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

作者：Diego Chowell, Luc G.T. Morris, Claud Grigg, Jeffrey K. Weber, Robert Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M. Kendall, David Requena, Nadeem Riaz, Benjamin D. Greenbaum, James M. Carroll, Edward B. Garon, David M. Hyman, Ahmet Zehir, David B. Solit, Michael F. Berger, Ruhong Zhou, Naiyer A. Rizvi, Timothy A. Chan · 发表于：Science · 年份：2017 · DOI：10.1126/science.aao4572 · 被引用次数：1195 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、vaccines and immunoinformatics approaches

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