Dendritic cells control tertiary lymphoid structure development and maintenance in cancer

@article{mattiuz2026dendritic,
  title = {{Dendritic cells control tertiary lymphoid structure development and maintenance in cancer}},
  author = {Raphaël Mattiuz and Jesse Boumelha and Emmanouil Aerakis and Jessica Le Bérichel and Pauline Hamon and László Halász and Abishek Balachandra Vaidya and Brian Y. Soong and Emir Radkevich and Hye Mi Kim and Matthew D. Park and Romain Donné and Leanna Troncoso and Rachel A. Kaplan and Clotilde Hennequin and Isaias Hernández-Verdín and Lucía López and Frederika Rentzeperis and Darwin D’souza and Medard Ernest and Ian MacFawn and Meriem Belabed and Guillaume Mestrallet and Étienne Humblin and Raphaël Merand and Samarth Hegde and Jean‐Christophe Lone and Giorgio Ioannou and Sinem Ozbey and Igor Figueiredo and Alexander Tepper and Hajer Merarda and Nadine Serhan and Maximilian M. Schaefer and Jinping An and Ray A. Ohara and Erika Nemeth and Simon Goldstein and Amanda M. Reid and Moataz Noureddine and Alexandra Tabachnikova and Giulia Maria Piperno and Maria Tsoumakidou and Jalal Uddin Ahmed and Alexandros D. Polydorides and Nina Bhardwaj and Amaia Lujambio and Zhihong Chen and Edgar Gonzalez‐Kozlova and Seunghee Kim‐Schulze and Joshua Brody and Michael Schotsaert and Christine Moussion and Sacha Gnjatic and Vladimir Roudko and Florent Ginhoux and KENNETH M. M. MURPHY and Catherine Sautès‐Fridman and Wolf H. Fridman and Brian D. Brown},
  journal = {Science},
  year = {2026},
  month = jul,
  doi = {10.1126/science.ady1678},
  url = {https://doi.org/10.1126/science.ady1678},
  note = {CC BY},
}

TY  - JOUR
TI  - Dendritic cells control tertiary lymphoid structure development and maintenance in cancer
AU  - Raphaël Mattiuz
AU  - Jesse Boumelha
AU  - Emmanouil Aerakis
AU  - Jessica Le Bérichel
AU  - Pauline Hamon
AU  - László Halász
AU  - Abishek Balachandra Vaidya
AU  - Brian Y. Soong
AU  - Emir Radkevich
AU  - Hye Mi Kim
AU  - Matthew D. Park
AU  - Romain Donné
AU  - Leanna Troncoso
AU  - Rachel A. Kaplan
AU  - Clotilde Hennequin
AU  - Isaias Hernández-Verdín
AU  - Lucía López
AU  - Frederika Rentzeperis
AU  - Darwin D’souza
AU  - Medard Ernest
AU  - Ian MacFawn
AU  - Meriem Belabed
AU  - Guillaume Mestrallet
AU  - Étienne Humblin
AU  - Raphaël Merand
AU  - Samarth Hegde
AU  - Jean‐Christophe Lone
AU  - Giorgio Ioannou
AU  - Sinem Ozbey
AU  - Igor Figueiredo
AU  - Alexander Tepper
AU  - Hajer Merarda
AU  - Nadine Serhan
AU  - Maximilian M. Schaefer
AU  - Jinping An
AU  - Ray A. Ohara
AU  - Erika Nemeth
AU  - Simon Goldstein
AU  - Amanda M. Reid
AU  - Moataz Noureddine
AU  - Alexandra Tabachnikova
AU  - Giulia Maria Piperno
AU  - Maria Tsoumakidou
AU  - Jalal Uddin Ahmed
AU  - Alexandros D. Polydorides
AU  - Nina Bhardwaj
AU  - Amaia Lujambio
AU  - Zhihong Chen
AU  - Edgar Gonzalez‐Kozlova
AU  - Seunghee Kim‐Schulze
AU  - Joshua Brody
AU  - Michael Schotsaert
AU  - Christine Moussion
AU  - Sacha Gnjatic
AU  - Vladimir Roudko
AU  - Florent Ginhoux
AU  - KENNETH M. M. MURPHY
AU  - Catherine Sautès‐Fridman
AU  - Wolf H. Fridman
AU  - Brian D. Brown
PY  - 2026
DA  - 2026/07/16
JO  - Science
DO  - 10.1126/science.ady1678
UR  - https://doi.org/10.1126/science.ady1678
AB  - Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood. Using spatial transcriptomics and multiplex imaging across various human tumors, we found an enrichment of mature dendritic cells (DC) expressing high levels of CCR7 in TLS, prompting us to investigate the role of DC in the formation and maintenance of TLS in solid tumors. To address this, we developed a novel murine model of non-small cell lung cancer (NSCLC) that forms mature TLS, containing B cell follicles with germinal centers and T cell zones with T follicular helper cells (T FH ) and TCF1 + PD-1 + progenitor exhausted CD8 + T cells (Tpex). Here we show that, during the early stages of tumor development, TLS formation relies on IFNγ-driven maturation of the conventional DC type 1 (cDC1) subset, their migration to tumor-draining lymph nodes (tdLN), and recruitment of activated T cells to the tumor site. As tumors progress, TLS maintenance becomes independent of T cell egress from tdLN, coinciding with a significant reduction of cDC1 migration to tdLN. Instead, mature cDC1 accumulate within intratumoral CCR7 ligand-enriched stromal hubs. Notably, timed depletion of cDC1 or disruption of their migration to these stromal hubs after TLS are formed alters TLS maintenance. Importantly, we found that cDC1-mediated antigen presentation to both CD4 + and CD8 + T cells and intact CD40 signaling, is critical for the maintenance of TLS, the preservation of the T FH cell pool, the formation of germinal center and the production of tumor-specific IgG antibodies. These findings underscore the key role of mature cDC1 in establishing and maintaining functional TLS within tumor lesions and highlight the potential for cDC1-targeting therapies as a promising strategy to enhance TLS function and improve anti-tumor immunity in patients with cancer.
SN  - 0036-8075
SN  - 0193-4511
SN  - 1095-9203
ER  -