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posted on 2025-04-02, 07:22 authored by Elisa Gobbini, Margaux Hubert, Anne-Claire Doffin, Anais Eberhardt, Léo Hermet, Danlin Li, Pierre Duplouye, Sarah Ghamry-Barrin, Justine Berthet, Valentin Benboubker, Maxime Grimont, Candice Sakref, Jimmy Perrot, Garance Tondeur, Olivier Harou, Jonathan Lopez, Bertrand Dubois, Stephane Dalle, Christophe Caux, Julie Caramel, Jenny Valladeau-Guilemond Description of the MELPREDICT cohort and design of experiments performed in the study.
Funding
European Society for Medical Oncology (ESMO)
Institut National Du Cancer (INCa)
Fondation ARC pour la Recherche sur le Cancer (ARC)
Ligue Contre le Cancer (French League Against Cancer)
LabEx DEvweCAN (DEVweCAN)
History
ARTICLE ABSTRACT
Dendritic cells (DC) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The type 1 conventional DC (cDC1) population is of particular interest because of its ability to cross-present antigens to CD8+ T cells. cDC1s also secrete cytokines that allow Th1 cell polarization and NK cell activation and recruitment. However, the spatial organization and specific functions of cDC1s in response to immunotherapy remain to be clearly characterized in human tumors. In this study, we used a multiplexed immunofluorescence analysis pipeline coupled with computational image analysis to determine the spatial organization of cDC1s in skin lesions from a cohort of patients with advanced melanoma treated with immune checkpoint inhibitors (ICI). For this, we performed a whole-slide image analysis of cDC1 infiltration, distribution, and spatial interaction with key immune partners such as CD8+ T cells and plasmacytoid DCs. We also analyzed LAMP3+ DCs, which correspond to a mature subset of tumor-infiltrating DCs. Distance and cell network analyses demonstrated that cDC1s exhibited a scattered distribution compared with tumor-infiltrating plasmacytoid DCs and LAMP3+ DCs, which were preferentially organized in dense areas with high homotypic connections. The proximity and interactions between CD8+ T cells and cDC1s were positively associated with the response to ICIs. In conclusion, our study unravels the complex spatial organization of cDC1s and their interactions with CD8+ T cells in lesions of patients with melanoma, shedding light on the pivotal role of these cells in shaping the response to ICIs.
