Dendritic cells control tertiary lymphoid structure development and maintenance in cancer

• 成果类型: Article
• 署名作者: Mattiuz, Raphael; Boumelha, Jesse; Aerakis, Emmanouil; Le Berichel, Jessica; Hamon, Pauline; Halasz, Laszlo; Vaidya, Abishek; Soong, Brian Y.; Radkevich, Emir; Kim, Hye Mi; Park, Matthew D.; Donne, Romain; Troncoso, Leanna; Kaplan, Rachel A.; Hennequin, Clotilde; Hernandez-Verdin, Isaias; Lopez, Lucia; Rentzeperis, Frederika; D'Souza, Darwin; Kaiza, Medard Ernest; MacFawn, Ian P.; Belabed, Meriem; Mestrallet, Guillaume; Humblin, Etienne; Merand, Raphael; Hegde, Samarth; Lone, Jean-Christophe; Ioannou, Giorgio; Ozbey, Sinem; Figueiredo, Igor; Tepper, Alexander; Merarda, Hajer; Serhan, Nadine; Schaefer, Maximilian M.; An, Jinping; Ohara, Ray A.; Nemeth, Erika; Goldstein, Simon; Reid, Amanda M.; Noureddine, Moataz; Tabachnikova, Alexandra; Piperno, Giulia Maria; Tsoumakidou, Maria; Ahmed, Jalal; Polydorides, Alexandros D.; Bhardwaj, Nina; Lujambio, Amaia; Chen, Zhihong; Gonzalez Kozlova, Edgar; Kim-Schulze, Seunghee; Brody, Joshua D.; Schotsaert, Michael; Moussion, Christine; Gnjatic, Sacha; Roudko, Vladimir; Ginhoux, Florent; Murphy, Kenneth M.; Sautes-Fridman, Catherine; Fridman, Wolf Herman; Brown, Brian D.; Marron, Thomas U.; Benvenuti, Federica; Cyster, Jason G.; Salmon, Helene; Bruno, Tullia C.; Joshi, Nikhil S.; Kamphorst, Alice O.; Merad, Miriam
• 署名单位: Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Universite Paris Cite; Sorbonne Universite; International Center for Genetic Engineering & Biotechnology (ICGEB); Icahn School of Medicine at Mount Sinai; Universidade de Lisboa; Universidade de Lisboa; Icahn School of Medicine at Mount Sinai; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Washington University (WUSTL); Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Roche Holding; Roche Holding USA; Genentech; Universite Paris Saclay; UNICANCER; Institut National de la Sante et de la Recherche Medicale (Inserm); Gustave Roussy; Icahn School of Medicine at Mount Sinai; UNICANCER; Universite PSL; Institut Curie; Yale University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady1678
• 发表日期: 2026-07-16
• 页码: eady1678
• 关键词: OPEN-LABEL; t-cells; lung-cancer; b-cells; immunotherapy; migration; chemokine; survival; differentiation; atezolizumab

摘要

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-gamma (IFN-gamma)-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 (TFH) 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.