美国加州大学旧金山分校Matthew H. Spitzer研究小组发现，人类区域淋巴结对癌症免疫治疗的动态CD8⁺T细胞反应在转移性淋巴结中被破坏。该项研究成果发表在2023年3月16日出版的《细胞》杂志上。

研究人员使用质谱仪、单细胞基因组学和多重离子束成像技术检查了人类头颈部鳞状细胞癌、区域性淋巴结（LN）和血液中的CD8⁺T细胞。研究人员确定了前体细胞耗竭的CD8⁺T细胞（Tpex），它们在未受影响的LN中大量存在，并与肿瘤中终末耗竭的细胞有克隆关系。在抗PD-L1免疫治疗后，未受影响的LN中的Tpex频率降低，但在树突状细胞和增殖的中间耗竭的CD8⁺T细胞（Tex-int）附近定位，与激活和分化一致。LN反应与循环中的Tex-int增加相吻合。在转移性LN中，这些反应标志受损，有免疫抑制细胞微环境。这些结果确定了LN在人类抗肿瘤免疫反应中的重要作用。

据悉，CD8⁺T细胞反应是抗肿瘤免疫的关键。虽然对肿瘤微环境进行了广泛的分析，但最近在小鼠中的研究发现LN的反应是至关重要的；然而，LN在人类癌症患者中的作用仍然未知。

附：英文原文

Title: Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes

Author: Maha K. Rahim, Trine Line H. Okholm, Kyle B. Jones, Elizabeth E. McCarthy, Candace C. Liu, Jacqueline L. Yee, Stanley J. Tamaki, Diana M. Marquez, Iliana Tenvooren, Katherine Wai, Alexander Cheung, Brittany R. Davidson, Vrinda Johri, Bushra Samad, William E. O’Gorman, Matthew F. Krummel, Annemieke van Zante, Alexis J. Combes, Michael Angelo, Lawrence Fong, Alain P. Algazi, Patrick Ha, Matthew H. Spitzer

Issue&Volume: 2023/03/16

Abstract: CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

DOI: 10.1016/j.cell.2023.02.021

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00164-2