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DOI 10.1126/science.ady1678

Медицинская библиотека · Science (New York, N.Y.) · 2026

Dendritic cells control tertiary lymphoid structure development and maintenance in cancer.

Mattiuz Raphaël, 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, Hernández-Verdin Isaias, López Lucía, Rentzeperis Frederika, D'Souza Darwin, Kaiza Medard Ernest, MacFawn Ian P, Belabed Meriem, Mestrallet Guillaume, Humblin Etienne, Merand Raphaël, 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, Sautès-Fridman Catherine, Fridman Wolf Herman, Brown Brian D, Marron Thomas U, Benvenuti Federica, Cyster Jason G, Salmon Hélène, Bruno Tullia C, Joshi Nikhil S, Kamphorst Alice O, Merad Miriam

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Аннотация

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 (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.

Для цитирования: Mattiuz Raphaël, 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, Hernández-Verdin Isaias, López Lucía, Rentzeperis Frederika, D'Souza Darwin, Kaiza Medard Ernest, MacFawn Ian P, Belabed Meriem, Mestrallet Guillaume, Humblin Etienne, Merand Raphaël, 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, Sautès-Fridman Catherine, Fridman Wolf Herman, Brown Brian D, Marron Thomas U, Benvenuti Federica, Cyster Jason G, Salmon Hélène, Bruno Tullia C, Joshi Nikhil S, Kamphorst Alice O, Merad Miriam. Dendritic cells control tertiary lymphoid structure development and maintenance in cancer.. Science (New York, N.Y.). 2026. DOI: 10.1126/science.ady1678.

Предметные рубрики MeSH

AnimalsDendritic CellsHumansTertiary Lymphoid StructuresMiceInterferon-gammaLymph NodesCD40 AntigensCarcinoma, Non-Small-Cell LungLung NeoplasmsChemokine CCL19Receptors, CCR7Antigen PresentationCell MovementHistocompatibility Antigens Class IGerminal CenterImmunoglobulin GT Follicular Helper CellsHistocompatibility Antigens Class IIMice, Inbred C57BL
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