Proximity-dependent labeling identifies dendritic cells that prime the antitumor CD4+ T cell response

Dendritic cells (DCs) are uniquely capable of transporting tumoral antigens to tumor-draining lymph nodes (tdLNs), where they initiate antitumor immunity and mediate checkpoint blockade immunotherapy. Despite recent advances, the full phenotype of the DCs involved in these processes has been difficult to establish. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identify individual DCs capable of presenting antigen to CD4+ T cells in the tdLN. These represent a small fraction of all DCs present in the tdLN and display a distinctive activated phenotype that includes production of cytokine IL-27, required for efficient T cell priming and tumor rejection. Tumor progression results in loss of effective priming of naïve CD4+ T cells, downstream of transcriptional changes in DCs that are manifested already when they arrive at the tdLN. Collectively, our data reveal temporal shift in DC activation status over the course of the antitumor immune response. ### Competing Interest Statement L.-F.L. is a scientific advisor for Elixiron Immunotherapeutics. G.D.V. has a U.S. patent on LIPSTIC technology (US10053683). G.D.V. is a scientific advisor for Vaccine Company, Inc.