Chudnovskiy et al. identified individual DCs presenting tumor-derived antigens to CD4+ T cells in a mouse melanoma model. Using LIPSTIC, a quantitative, CD40-driven, proximity-based labeling protocol that can identify T cell-engaged DCs at the individual cell level (combined with single-cell transcriptomics), they found that tumor antigen-presenting DCs had hyperactivated transcriptional phenotypes, comprised a relatively minor fraction of all DCs (approx.15%), and secreted IL-27. Individual DCs interacted with tumor-specific CD4+ and CD8+ T cells in the tdLNs, and with CD4+ T cells in the TME, which was enhanced by the addition of ICB.
Contributed by Katherine Turner
ABSTRACT: Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4(+) T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4(+) and CD8(+) tumor-specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.
Author Info: (1) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (2) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (3) Laboratory o
Author Info: (1) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (2) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (3) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (4) Broad Institute of MIT and Harvard, Cambridge, MA, USA. Harvard School of Dental Medicine, Harvard University, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (5) School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. (6) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (7) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (8) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (9) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (10) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA. (11) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (12) Laboratory of Synthetic Immunology, Oncology and Immunology Section, Department of Surgery Oncology and Gastroenterology, University of Padua, Padua, Italy. Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. (13) School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. (14) Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. (15) Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA.
