Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immunity. 2023 Jan 10;56(1):93-106.e6. doi: 10.1016/j.immuni.2022.12.001. Epub 2022 Dec 26.
Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8 T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8 T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39 CD8 T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39 CD8 T cells. Higher baseline frequency of CD39 CD8 T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39 CD8 T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8 T cells in human lung cancer.
需要更准确地鉴定抗肿瘤 T 细胞，以推进癌症免疫疗法。CD39 的表达是肿瘤反应性 CD8 T 细胞的一个很有前途的替代标志物。在这里，我们全面分析了人类肺癌中 CD39 的表达。CD39 的表达富集了具有耗竭、肿瘤反应性和克隆扩增特征的 CD8 T 细胞。对 440 个肺癌生物样本的流式细胞术分析显示，CD39 CD8 T 细胞与肿瘤特征（如程序性死亡配体 1（PD-L1）、肿瘤突变负担和驱动突变）之间存在微弱关联。免疫检查点阻断（ICB）而非细胞毒性化疗增加了肿瘤内 CD39 CD8 T 细胞。较高的基线 CD39 CD8 T 细胞频率可改善 ICB 治疗的临床结局。此外，在一项非小细胞肺癌的 III 期临床试验中，CD39 CD8 T 细胞的基因特征预测了 ICB 治疗的获益，但不能预测化疗的获益。这些发现强调了 CD39 作为人类肺癌中肿瘤反应性 CD8 T 细胞的替代标志物。
