Gaffney Stephen G, Perry Elizabeth B, Chen Ping-Min, Greenstein Andrew, Kaech Susan M, Townsend Jeffrey P
Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.
Gilead Sciences, Foster City, CA, USA.
Oncotarget. 2019 Jul 16;10(44):4532-4545. doi: 10.18632/oncotarget.27027.
Immunotherapies targeting immune checkpoint proteins CTLA-4, PD-1, and PD-L1 have saved lives, but these therapies have only been effective in some patients. Patients positive for expression of immune checkpoint proteins in the tumor microenvironment show better response to immune checkpoint inhibitors. Consequently, knowledge of which genes are consistently expressed in lymphocytes within the tumor microenvironment can convey potentially effective and complementary new immunotherapy targets. We identified 54 genes that have higher co-expression with the pan T-cell marker than or . In a dataset of 26 patients who received anti-PD-1 therapy, we observed that co-expression between and was higher among responders than non-responders, supporting our correlation-based approach. The genes highlighted in these analyses, which include , , , and , warrant further investigation of their therapeutic potential. We analyzed and ranked genes that were co-expressed with the pan T-cell marker in 9,601 human tumors, spanning 31 cancer types. To further identify targets that may be complementary to existing PD-1 therapy, we examined and ranked genes with high co-expression and relatively low co-expression.
靶向免疫检查点蛋白CTLA-4、PD-1和PD-L1的免疫疗法挽救了许多生命，但这些疗法仅对部分患者有效。肿瘤微环境中免疫检查点蛋白表达呈阳性的患者对免疫检查点抑制剂的反应更好。因此，了解哪些基因在肿瘤微环境中的淋巴细胞中持续表达，可能会带来潜在有效的补充性新免疫治疗靶点。我们鉴定出54个与泛T细胞标志物共表达水平高于或等于[具体比较对象]的基因。在一个包含26例接受抗PD-1治疗患者的数据集里，我们观察到[具体基因对]之间的共表达在应答者中高于无应答者，这支持了我们基于相关性的方法。这些分析中突出的基因，包括[具体基因列表]，值得进一步研究它们的治疗潜力。我们分析并对9601个人类肿瘤（涵盖31种癌症类型）中与泛T细胞标志物共表达的基因进行了排名。为了进一步确定可能与现有PD-1治疗互补的靶点，我们检查并对共表达水平高且相对低[具体基因]共表达的基因进行了排名。
