小柯机器人

美国斯坦福大学Ansuman T. Satpathy和纪念斯隆凯瑟琳研究中心Andrew Chow团队合作，利用谱系追踪揭示在免疫检查点封锁(ICB)期间克隆祖细胞和肿瘤特异性T细胞的长期持久性。2023年3月30日，国际知名学术期刊《癌细胞》发表了这一成果。

他们报告了一项来自31个组织区域的187,650个T细胞的单细胞RNA和T细胞受体测序(scRNA/TCR-seq)分析，包括肿瘤、邻近正常组织和淋巴结(LN)，来自3例 ICB后的非小细胞肺癌患者。存活癌细胞的区域富集耗尽的CD8+ T细胞、调节性CD4+ T细胞(Treg)和滤泡辅助CD4+ T细胞(TFH)。

结合新抗原特异性测定，在组织中跟踪T细胞克隆型，揭示TFH和肿瘤特异性衰竭CD8+ T细胞在肿瘤引流LNs中与TCF7+ SELL+祖细胞克隆相关，CD8+ T、Treg和TFH细胞的渐向性衰竭轨迹与肿瘤微环境接近。最后，对肿瘤特异性CD8+和CD4+ T细胞克隆的纵向跟踪显示，ICB治疗后外周血中持续存在数年。

附：英文原文

Title: Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade

Author: Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter, Marissa Mattar, Hira Rizvi, Hyung Jun Woo, Nisargbhai Shah, Evelyn M. Nguyen, Fathema Z. Uddin, Alvaro Quintanal-Villalonga, Joseph M. Chan, Parvathy Manoj, Viola Allaj, Marina K. Baine, Umesh K. Bhanot, Mala Jain, Irina Linkov, Fanli Meng, David Brown, Jamie E. Chaft, Andrew J. Plodkowski, Mathieu Gigoux, Helen H. Won, Triparna Sen, Daniel K. Wells, Mark T.A. Donoghue, Elisa de Stanchina, Jedd D. Wolchok, Brian Loomis, Taha Merghoub, Charles M. Rudin, Andrew Chow, Ansuman T. Satpathy

Issue&Volume: 2023-03-30

Abstract: Paired single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) has allowedfor enhanced resolution of clonal T cell dynamics in cancer. Here, we report a scRNA/TCR-seqanalysis of 187,650 T cells from 31 tissue regions, including tumor, adjacent normaltissues, and lymph nodes (LN), from three patients with non-small cell lung cancerafter immune checkpoint blockade (ICB). Regions with viable cancer cells are enrichedfor exhausted CD8+ T cells, regulatory CD4+ T cells (Treg), and follicular helper CD4+ T cells (TFH). Tracking T cell clonotypes across tissues, combined with neoantigenspecificity assays, reveals that TFH and tumor-specific exhausted CD8+ T cells are clonally linked to TCF7+ SELL+ progenitors in tumor draining LNs, and progressive exhaustion trajectories of CD8+ T, Treg, and TFH cells with proximity to the tumor microenvironment. Finally, longitudinaltracking of tumor-specific CD8+ and CD4+ T cell clones reveals persistence in the peripheral blood for years after ICB therapy.

DOI: 10.1016/j.ccell.2023.03.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00082-X

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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