First Author | Chudnovskiy A | Year | 2024 |
Journal | Sci Immunol | Volume | 9 |
Issue | 100 | Pages | eadq8843 |
PubMed ID | 39365874 | Mgi Jnum | J:360907 |
Mgi Id | MGI:7782826 | Doi | 10.1126/sciimmunol.adq8843 |
Citation | Chudnovskiy A, et al. (2024) Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4(+) T cell response. Sci Immunol 9(100):eadq8843 |
abstractText | 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. |