Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy
Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy
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DOI：
10.1016/j.ccell.2019.01.003
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发表时间：
2019-02-11
期刊：
影响因子：
50.3
通讯作者：
Wilmott, James S.
中科院分区：
文献类型：
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作者：
Gide, Tuba N.;Quek, Camelia;Wilmott, James S.
癌症免疫疗法为有反应的患者提供了生存益处，但许多患者没有反应。识别治疗反应和耐药性的生物学是优化药物选择和改善患者结局的优先事项。我们对来自接受抗PD-1单药治疗（n = 63）或抗PD-1和抗CTLA-4联合治疗（n = 57）的黑色素瘤患者的158例肿瘤活检进行了转录组学和免疫分析。这些数据在两种治疗的应答者中鉴定了活化的T细胞特征和T细胞群。进一步的质谱细胞术分析鉴定了EOMES（+）CD 69（+）CD 45 RO（+）效应记忆T细胞表型，与无应答者相比，其在联合免疫疗法的应答者中显著更丰富（n = 18）。该人群的基因表达谱与单药治疗患者的无进展生存期延长和两种治疗的肿瘤缩小程度增加相关。
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES(+)CD69(+)CD45RO(+) effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments.