转移性黑色素瘤中CTLA-4阻断反应的基因组相关性
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma
抗CTLA-4抗体（ipilimumab）对转移性黑色素瘤有效，但预测疗效的标志物尚不明确。研究分析了110例患者治疗前肿瘤活检的全外显子数据及其中40例的转录组数据。总体突变负荷、新抗原负荷和免疫微环境中细胞溶解标志物的表达与临床获益显著相关，但未发现能预测应答的复发性新抗原肽序列。提示需更大规模的整合分子分析来找到可靠的疗效预测因子。
为什么推荐给您：较早的队列研究，揭示突变负荷与新抗原负荷同CTLA-4阻断获益相关，属重要机制发现但非全新疗法。
不需要生物学背景，多打比方
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摘要Abstract
Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.