biostudies-literatureChudnovskiy ANIAID NIH HHSHSRD VAeadq8843https://www.ebi.ac.uk/biostudies/studies/S-EPMC12419230biostudies-literatureUnknown9(100)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 responsibleScience immunologyProximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4<sup>+</sup> T cell response.PMC12419230DP1 AI144248R21 AI163813R21 AI178396R01 AI108651SDP 10-044Victora GDSade-Feldman MPhillips BKPae JBortolatto JPasqual GChudnovskiy ANakandakari-Higa SMesin LCastro TBRLu LFHacohen NSchweitzer LDCui ALin CHfalseProximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4<sup>+</sup> T cell response.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 responsible2024-01-01T00:00:00Z2024 Oct2026-06-02T17:40:30.374Z2026-04-18T03:11:25.656ZS-EPMC124192303936587410.1126/sciimmunol.adq8843