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Publication : Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4(+) T cell response.

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.
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