{"doi":"10.1016/j.cell.2023.02.021","title":"Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes","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.","journal":"Cell","year":2023,"id":314780,"datarank":4.938692758670286,"base_score":6.045005314036012,"endowment":6.045005314036012,"self_citation_contribution":0.906750797105402,"citation_network_contribution":4.031941961564884,"self_endowment_contribution":0.906750797105402,"citer_contribution":4.031941961564884,"corpus_percentile":null,"corpus_rank":null,"citation_count":421,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03708224"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":823505,"name":"Trine Line Hauge Okholm","orcid":"0000-0002-2779-4029","position":1,"is_corresponding":false},{"id":1014072,"name":"Kyle B. 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