美国西奈山伊坎医学院Miriam Merad课题组探明了树突状细胞在肿瘤中控制三级淋巴结构的发育和维持。该研究于2026年7月16日发表于国际一流学术期刊《科学》杂志上。

通过对人类肿瘤的空间转录组学和多重成像，该课题组研究人员发现CCR7+成熟树突状细胞（DC）在TLSs中积累。在形成成熟TLSs的无主题非小细胞肺癌模型中，研究小组发现早期TLSs的发展需要干扰素-γ (IFN-γ)驱动的1型常规树突状细胞（cDC1）成熟、向肿瘤引流淋巴结（tdLNs）的迁移和T细胞募集。随着肿瘤的进展，TLSs独立于tdLN T细胞的输出而持续存在，与肿瘤内CCL19基质中心的cDC1积累相一致。在那里，cdc1 -主要组织相容性复合体1类（MHC-I）和-MHC-II伴随抗原呈递，以及CD40信号、维持TLS、T滤泡辅助（TFH）细胞池、生发中心和肿瘤特异性免疫球蛋白G （IgG）。这些发现强调了局部成熟cDC1s作为关键的TLS协调者和增强抗肿瘤TLS功能的潜在靶点。

据悉，三级淋巴结构（TLSs）与免疫治疗反应有关，但控制其形成和维持的机制尚不清楚。

附：英文原文

Title: Dendritic cells control tertiary lymphoid structure development and maintenance in cancer

Author: Raphal Mattiuz, Jesse Boumelha, Emmanouil Aerakis, Jessica Le Berichel, Pauline Hamon, Laszlo Halasz, Abishek Vaidya, Brian Y. Soong, Emir Radkevich, Hye Mi Kim, Matthew D. Park, Romain Donne, Leanna Troncoso, Rachel A. Kaplan, Clotilde Hennequin, Isaias Hernández-Verdin, Lucía López, Frederika Rentzeperis, Darwin D’Souza, Medard Ernest Kaiza, Ian P. MacFawn, Meriem Belabed, Guillaume Mestrallet, Etienne Humblin, Raphal Merand, Samarth Hegde, Jean-Christophe Lone, Giorgio Ioannou, Sinem Ozbey, Igor Figueiredo, Alexander Tepper, Hajer Merarda, Nadine Serhan, Maximilian M. 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 D. Brody, Michael Schotsaert, Christine Moussion, Sacha Gnjatic, Vladimir Roudko, Florent Ginhoux, Kenneth M. Murphy, Catherine Sautès-Fridman, Wolf Herman Fridman, Brian D. Brown, Thomas U. Marron, Federica Benvenuti, Jason G. Cyster, Hélène Salmon, Tullia C. Bruno, Nikhil S. Joshi, Alice O. Kamphorst, Miriam Merad

Issue&Volume: 2026-07-16

Abstract: 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.

DOI: ady1678

Source: https://www.science.org/doi/10.1126/science.ady1678

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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