美国默克公司Alexandra Snyder等研究人员合作发现，种系HLA谱不能预测不同类型实体瘤的pembrolizumab单药疗效。相关论文于2022年1月4日在线发表在《免疫》杂志上。

研究人员评估了I类和II类人类白细胞抗原（HLA）的基因型、杂合性和多样性对pembrolizumab疗效的影响。纳入了17项跨越8种肿瘤类型的pembrolizumab临床试验和一项晚期实体瘤患者的篮子试验（n>3,500）。一个定制的基因分型阵列被用于对种系DNA的基因分型。无论是在所评估的每种肿瘤类型中，还是在所有患者中，第一类位点的HLA多样性（通过杂合度和进化分歧衡量）与改善对pembrolizumab的反应没有关系。同样，在考虑到进行的测试次数后，每个I类和II类基因的HLA杂合度与对pembrolizumab的反应没有关系。

在这个数据集中，没有发现HLA基因型和对pembrolizumab的反应之间有结论性的关联。单纯的胚胎HLA基因型或多样性不是决定对pembrolizumab反应的重要独立因素，不应该用于接受pembrolizumab治疗患者的临床决策。

附：英文原文

Title: Germline HLA landscape does not predict efficacy of pembrolizumab monotherapy across solid tumor types

Author: Aparna Chhibber, Lingkang Huang, Hong Zhang, Jialin Xu, Razvan Cristescu, Xiaoqiao Liu, Devan V. Mehrotra, Judong Shen, Peter M. Shaw, Matthew D. Hellmann, Alexandra Snyder

Issue&Volume: 2022-01-04

Abstract: We evaluated the impact of class I and class II human leukocyte antigen (HLA) genotypes,heterozygosity, and diversity on the efficacy of pembrolizumab. Seventeen pembrolizumabclinical trials across eight tumor types and one basket trial in patients with advancedsolid tumors were included (n > 3,500 analyzed). Germline DNA was genotyped usinga custom genotyping array. HLA diversity (measured by heterozygosity and evolutionarydivergence) across class I loci was not associated with improved response to pembrolizumab,either within each tumor type evaluated or across all patients. Similarly, HLA heterozygosityat each class I and class II gene was not associated with response to pembrolizumabafter accounting for the number of tests conducted. No conclusive association betweenHLA genotype and response to pembrolizumab was identified in this dataset. GermlineHLA genotype or diversity alone is not an important independent determinant of responseto pembrolizumab and should not be used for clinical decision-making in patients treatedwith pembrolizumab.

DOI: 10.1016/j.immuni.2021.12.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00542-2