CD8+ T细胞反应对于抗肿瘤免疫至关重要。虽然在肿瘤微环境中进行了广泛的剖析，但最近的小鼠研究发现淋巴结（LNs）中的反应是必不可少的；然而，在人类癌症患者中，淋巴结的作用尚不清楚。我们使用质谱细胞术、单细胞基因组学和多重离子束成像技术，检查了头颈部鳞状细胞癌、区域淋巴结和血液中的CD8+ T细胞。我们发现在未涉及LN中丰富存在一种祖细胞疲惫的CD8+ T细胞（Tpex），这些细胞与肿瘤中的末端疲惫细胞在克隆上相关。在抗PD-L1免疫治疗后，在未涉及的LN中，Tpex的频率减少，但靠近树突状细胞和增殖中间疲惫CD8+ T细胞（Tex-int）定位，符合激活和分化。LN反应与循环的Tex-int增加相一致。在转移的LN中，这些反应的特点受到了损害，存在免疫抑制的细胞区。我们的结果确定了淋巴结在人类抗肿瘤免疫反应中的重要作用。版权所有©2023 The Authors。Elsevier Inc.保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.