학술논문
Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.
Document Type
article
Author
Rahim, Maha; Okholm, Trine; Jones, Kyle; McCarthy, Elizabeth; Liu, Candace; Yee, Jacqueline; Tamaki, Stanley; Marquez, Diana; Tenvooren, Iliana; Wai, Katherine; Davidson, Brittany; Johri, Vrinda; Combes, Alexis; Angelo, Michael; Fong, Lawrence; OGorman, William; Krummel, Matthew; Ha, Patrick; van Zante, Annemieke; Algazi, Alain; Spitzer, Matthew; Samad, Bushra; Cheung, Alexander
Source
Cell. 186(6)
Subject
Language
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.