Dendritic cells control tertiary lymphoid structure development and maintenance in cancer

作者：Raphaël Mattiuz, Jesse Boumelha, Emmanouil Aerakis, Jessica Le Bérichel, Pauline Hamon, László Halász, Abishek Vaidya, Brian Y. Soong, Emir Radkevich, Hye Mi Kim, Matthew D. Park, Romain Donné, Leanna Troncoso, Rachel A. Kaplan, C. Hennequin, Isaias Hernández-Verdín, Lucía López, Frederika Rentzeperis, Darwin D’souza, Medard Ernest, Ian P. MacFawn, Meriem Belabed, Guillaume Mestrallet, Étienne Humblin, Raphaël Merand, Samarth Hegde, Jean‐Christophe Lone, Giorgio Ioannou, Sinem Ozbey, Igor Figueiredo, Alexander Tepper, Hajer Merarda, Nadine Serhan, Maximilian Schaefer, Jinping An, Ray A. Ohara, Erika Nemeth, Simon Goldstein, Amanda M. Reid, Moataz Noureddine, Alexandra Tabachnikova, Giulia Maria Piperno, Maria Tsoumakidou, Jalal Ahmed, Alexandros D. Polydorides, Nina Bhardwaj, Amaia Lujambio, Zhihong Chen, Edgar Gonzalez‐Kozlova, Seunghee Kim‐Schulze, Joshua Brody, Michael Schotsaert, Christine Moussion, Sacha Gnjatic, Vladimir Roudko, Florent Ginhoux, Kenneth M. Murphy, Catherine Sautès-Fridman, Wolf H. Fridman, Brian D. Brown, Thomas U. Marron, Federica Benvenuti, Jason G. Cyster, Hélène Salmon, Tullia C. Bruno, Nikhil S. Joshi, Alice O. Kamphorst, Miriam Mérad · 发表于：Science · 年份：2026 · DOI：10.1126/science.ady1678 · 被引用次数：6 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

Tertiary lymphoid structures (TLSs) are associated with immunotherapy response, yet the mechanisms controlling their formation and maintenance remain unclear. Using spatial transcriptomics and multiplex imaging across human tumors, we found that CCR7 + mature dendritic cells (DCs) accumulate in TLSs. In a mouse non–small cell lung cancer model that forms mature TLSs, we show that early TLS development requires interferon-γ (IFN-γ)–driven type 1 conventional dendritic cell (cDC1) maturation, migration to tumor-draining lymph nodes (tdLNs), and T cell recruitment. As tumors progress, TLSs persist independently of tdLN T cell egress, coinciding with cDC1 accumulation within intratumoral CCL19 stromal hubs. There, cDC1–major histocompatibility complex class 1 (MHC-I) and –MHC-II concomitant antigen presentation, along with CD40 signaling, sustain TLS, T follicular helper (T FH ) cell pool, germinal centers, and tumor-specific immunoglobulin G (IgG). These findings highlight local mature cDC1s as key TLS orchestrators and potential targets to enhance antitumor TLS function.