小柯机器人

美国纪念斯隆凯特琳癌症中心Charles M. Rudin，Taha Merghoub和Andrew Chow共同合作近期取得重要工作进展，他们研究发现外核苷酸酶CD39鉴定肿瘤反应性CD8⁺ T细胞并预测免疫检查点阻断在人肺癌中的功效。相关研究结果2022年12月26日在线发表于《免疫》杂志上。

据介绍，需要改进抗肿瘤T细胞的鉴定方法，以推进癌症的免疫治疗。CD39表达是肿瘤反应性CD8⁺ T细胞的一种有前景的替代物。

研究人员全面分析了CD39在人类肺癌中的表达。CD39的表达富集于CD8⁺ T细胞，具有衰竭、肿瘤反应性和克隆性扩张的特征。440个肺癌生物样本的流式细胞术显示CD39⁺CD8⁺ T细胞与肿瘤特征（如程序性死亡配体1（PD-L1）、肿瘤突变负荷和驱动突变）之间的弱关联。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。CD39⁺CD8⁺ T细胞的较高基线频率提高了ICB治疗的临床疗效。

此外，在一项非小细胞肺癌的III期临床试验中，CD39⁺CD8⁺ T细胞的基因标记预测了ICB而非化疗的益处。这些发现突出了CD39可以作为人类肺癌中肿瘤反应性CD8+T细胞的代表。

附：英文原文

Title: The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer

Author: Andrew Chow, Fathema Z. Uddin, Michael Liu, Anton Dobrin, Barzin Y. Nabet, Levi Mangarin, Yonit Lavin, Hira Rizvi, Sam E. Tischfield, Alvaro Quintanal-Villalonga, Joseph M. Chan, Nisargbhai Shah, Viola Allaj, Parvathy Manoj, Marissa Mattar, Maximiliano Meneses, Rebecca Landau, Mariana Ward, Amanda Kulick, Charlene Kwong, Matthew Wierzbicki, Jessica Yavner, Jacklynn Egger, Shweta S. Chavan, Abigail Farillas, Aliya Holland, Harsha Sridhar, Metamia Ciampricotti, Daniel Hirschhorn, Xiangnan Guan, Allison L. Richards, Glenn Heller, Jorge Mansilla-Soto, Michel Sadelain, Christopher A. Klebanoff, Matthew D. Hellmann, Triparna Sen, Elisa de Stanchina, Jedd D. Wolchok, Taha Merghoub, Charles M. Rudin

Issue&Volume: 2022-12-26

Abstract: 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. Flowcytometry 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 mutationburden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxicchemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a genesignature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinicaltrial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactiveCD8+ T cells in human lung cancer.

DOI: 10.1016/j.immuni.2022.12.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00605-7

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