Intratumoral cDC1–T cell clusters serve as sites of local costimulation to enhance CTL-mediated tumor rejection
Year: 2026
Type: article
Abstract: Summary T cells are essential for anti-tumor immunity, but their ability to eliminate tumors depends on coordinated interactions with type 1 conventional dendritic cells (cDC1s). While cDC1s are known for cross-presenting tumor-derived antigens in lymph nodes to prime CD8+ T cells, their role within the tumor itself remains less well understood. Here, we use the Skin Tumor Array by Micro-Poration (STAMP) model to investigate how cDC1-T cell interactions shape immune responses and influence tumor fate. Our data reveal that it is the spatial distribution of both cDC1s and T cells that determines whether a tumor can be rejected. We defined three primary immunotypes based on the spatial distribution of T cells and cDC1s: T cell-inflamed/dendritic cell-inflamed (TC-In/DC-In) tumors, where T cells and cDC1s co-infiltrate the tumor; T cell-inflamed/dendritic cell-excluded (TC-In/DC-Ex) tumors, where T cells infiltrate but cDC1s remain at the periphery; and T cell-excluded/dendritic cell-excluded (TC-Ex/DC-Ex) tumors, which lack both cDC1 and T cell infiltration. Notably, TC-In/DC-In tumors are more likely to undergo rejection, whereas TC-In/DC-Ex tumors persist despite T cell infiltration. Within TC-In/DC-In tumors, cDC1s engage in direct interactions with T cells, upregulate co-stimulatory molecules, and sustain effector T cell responses, while cDC1s in TC-In/DC-Ex tumors express higher migration-associated genes, suggesting a propensity to exit the tumor. We further show that chemokine modulation, particularly through CXCL9, CCL5, and XCL1, can reshape immune infiltration patterns to promote intra-tumoral cDC1-T cell clustering and improve tumor rejection. These findings underscore the unexpectedly important role of cDC1 positioning and function in sustaining effective anti-tumor immunity and highlight spatially organized cDC1-T cell clusters as critical hubs for local T cell activation.
Authors: Catherine B. Carbone, Markus Brown, Camille-Charlotte Balança, Anthony C. Antonelli, Shiuh-Ming Luoh, Karl L. Banta, Vincent Rouilly, Ximo Pechuan-Jorge, Guadalupe Ortiz-Muñoz, Jeanne Cheung, Ines Marin, Ellen Duong, Aditya A. Anand, Rajiv Jesudason, Caleb K. Chan, Anugraha Rajagopalan, Justin T. Gibson, Amanda Lorentzian, Elisa Penna, Jian Jiang, Linda Rangell, Yuxin Liang, Jérémie Decalf, Rosa Barreira da Silva, Ying Zhu, Shannon J. Turley, Geraldine A. Strasser, Sandra Rost, Shomyseh Sanjabi, James Ziai, Kathryn Geiger-Schuller, Lélia Delamarre, Ira Mellman, Christine Moussion
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4410717567