Clonal sharing and plasticity of follicular CD4 + T cells across lymph nodes and tumors in non-small cell lung cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: Tumor-invaded lymph nodes (LNs) are critical but poorly studied hubs of anti-tumor immunity. Using single-cell transcriptome, clonotype, and chromatin profiling, we analyze CD4 + T cells from blood, LNs, and tumors of NSCLC patients. LNs and tumors are enriched in follicular regulatory T cells (Treg-Tfr), follicular-like conventional T cells (Tconv-Tfh and Tconv-CXCL13), and tissue-resident Tregs (Treg-Trm). These populations are predicted to share a transcriptional program of activation and tissue adaptation, driven by BATF. Additionally, these subsets show extensive LN-tumor clonal sharing, indicating recirculation, and are enriched in transcriptional signatures of tumor reactivity. Treg-Tfr cells function as progenitors bifurcating into Treg-Trm or ex-Tregs with a Tfh-like CXCL13+ effector phenotype. Follicular subsets in LNs and tumors are transcriptionally and epigenetically similar and localize in germinal-center-like niches. Overall, tumor-invaded LNs and tumors coordinate the generation and maintenance of tumor-reactive CD4+ lineages, identifying highly plastic follicular T cells as therapeutic checkpoints to reinforce anti-tumor responses. To provide additional insights into the biology of CD4 + T cells in cancer, here the authors report a multi-omics analysis of CD4 + T cells from matched blood, tumor invaded lymph nodes (LNs), and tumor tissues of patients with non-small cell lung cancer, showing that tumor-invaded LNs and tumors harbor clonally linked and plastic follicular CD4+T cell subsets.
Source: Nature Communications
Authors: Jimena Tosello Boari, Wilfrid Richer, Yoann Missolo-Koussou, Elisa Bonnin, Sebastien Lemoine, Marco Antônio Pretti, Rodrigo Nalio Ramos, Jeremy Mesple, Jordan Denizeau, Sylvain Baulande, Mylène Bohec, Sonia Lameiras, Philippe Martin, Rafael Mena Osuna, Wenjie Sun, Marine Lefevre, Agathe Seguin-Givelet, Christine Sedlik, Filipa Ramos, Saumya Kumar, Leïla Perié, Luis Graça, Olivier Lantz, Edith Borcoman, Nicolas Girard, Joshua J. Waterfall, Eliane Piaggio
Institutions: Inserm, Université Paris-Est Créteil, Université Paris Sciences et Lettres, Institut Mondor de Recherche Biomédicale, Institut Curie, Universidade de São Paulo, D’Or Institute for Research and Education, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Centre National de la Recherche Scientifique, Sorbonne Université, Physique des Cellules et Cancers, University of Lisbon, Gulbenkian Institute for Molecular Medicine, Medizinische Hochschule Hannover, Helmholtz Centre for Infection Research, Centre for Individualised Infection Medicine, Université de Versailles Saint-Quentin-en-Yvelines
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7203819217
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