O02
A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity
MEISER P. 1, KNOLLE M. 2,3,4, HIRSCHBERGER A. 1, DE ALMEIDA G. 5,6, BAYERL F. 1, LACHER S. 1, PEDDE A. 1, FLOMMERSFELD S. 7, STÖGBAUER F. 9, ANTON M. 1, WIRTH M. 8, STEIGER K. 9,10,11, BUCHHOLZ V. 7, WOLLENBERG B. 8, ZIELINSKI C. 12,13, BRAREN R. 3, RÜCKERT D. 2,14, KNOLLE P. 1,15, KAISSIS G. 2,3,4, BÖTTCHER J. 1
1 Institute of Molecular Immunology, Technical University Munich, Munich, Germany; 2 Institute for Artificial Intelligence in Medicine & Healthcare, Technical University Munich, Munich, Germany; 3 Institute for Diagnostic and Interventional Radiology, Technical University Munich, Munich, Germany; 4 Department of Computing, Imperial College London, London, United Kingdom; 5 Institute of Animal Physiology and Immunology, Technical University Munich, Munich, Germany; 6 Institute of Virology, Technical University Munich, Munich, Germany; 7 Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany; 8 Department of Otolaryngology Head and Neck Surgery, Technical University Munich, Munich, Germany; 9 Institute of Pathology, Technical University Munich, Munich, Germany; 10 Comparative Experimental Pathology, Technical University Munich, Munich, Germany; 11 German Cancer Consortium, Munich, Germany; 12 Department of Infection Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany; 13 Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany; 14 Chair for Artificial Intelligence in Medicine and Healthcare, Technical University Munich, Munich, Germany; 15 German Center for Infection Research, Munich, Germany
Type 1 conventional dendritic cells (cDC1) are thought to support T cell responses within tumor tissue, but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8+ T cell clustering as a critical determinant of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1+CD8+ T cells. We identify a distinct population of immunostimulatory CCR7neg cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for CD8+ T cell differentiation and expansion within tumors and promotes cancer immune control. Similarly, in human cancers, CCR7negcDC1 interact with T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of anti-cancer T cell responses orchestrated by MHCIIhiCCR7neg cDC1 that determines protective versus ineffective anti-cancer immunity and could be exploited for cancer therapy.