Data from Intratumoral Three-Cell-Type Clusters Are a Conserved Feature of Endogenous Antitumor Immunity
Year: 2026
Type: other
Abstract: Effective antitumor immunity ultimately depends on the priming and activation of tumor-specific cytotoxic CD8+ T cells; however, the role of intratumoral cell–cell immune interactions remains incompletely understood. Recent work has revealed that the temporospatial co-localization of dendritic cells (DC), T helper (Th) cells, and cytotoxic T lymphocytes (CTL) within the tumor immune microenvironment following immune checkpoint blockade correlates with clinical response. In this study, we report the integration of more than 1 million spatially resolved single-cell profiles across six spatial proteomic and transcriptomic assays, which demonstrated that DC:Th:CTL three-cell-type clusters were common even in immunotherapy-naïve and highly desmoplastic tumors, such as fibrolamellar carcinoma and pancreatic ductal adenocarcinoma. We found that these immune triads were enriched for functionally important type 1 conventional DC, mature DCs enriched in immunoregulatory molecules, CXCL13+ Th, and GZMK+ effector CTL phenotypes. Subsequent multiplex immunofluorescence imaging of more than 450 primary pancreatic ductal adenocarcinoma tumors showed that the density of antigen-presenting cell:Th:CTL three-cell-type clusters was correlated with intratumoral T-cell clonal expansion and improved overall survival. These findings suggest that DC:Th:CTL triads are conserved across solid tumors and highlight the importance of intratumoral spatial niches in mediating endogenous antitumor immunity.
Authors: Sheela R. Damle, Jason A. Carter, Kristin E. Goodsell, Jose M.B. Pineda, Lindsay K. Dickerson, Xiuyun Jiang, Jacqueline L. Mudd, Thomas Walsh, Heidi L. Kenerson, Jack Cernak, Sardar Shahmir B. Chauhan, Emily Beirne, Sujata Jana, Amanda L. Koehne, Kiran R. Vij, Marianna B. Ruzinova, Raymond Yeung, Shreeram Akilesh, Eric A. Collisson, Ryan C. Fields, I. Nicholas Crispe, Venu G. Pillarisetty
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7127395061