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- W4313405761 abstract "Abstract An effective anti-tumor response requires activation of both CD4 helper T cells (through MHC-II) and CD8 cytotoxic T cells (through MHC-I). Activation of tumor-specific T cells depends on tumor antigen presentation by DCs. However, it is known that the tumor microenvironment largely suppresses immune responses. The focus of our study is to characterize the functional status of DCs in tumor-draining lymph nodes (TDLN) and to identify the mechanisms that lead to defective tumor antigen presentation. We transplanted tumors into the flank of mice and analyzed DCs from TDLN and contralateral non-draining lymph nodes (NDLN). Cross-presentation of OVA to CD8 T cells was not suppressed in TDLN either in vivo or ex vivo. However, both in vivo and ex vivo CD4 T cell activation by DCs from TDLNs was defective. Subset analysis revealed that both migratory and resident DCs in TDLN show a less mature phenotype as compared to their counterparts isolated from NDLN. Functional assays revealed defects in antigen uptake by DCs from TDLN. Interestingly, DCs in TDLN also showed poor removal of the Invariant-chain CLIP peptide from the MHC-II peptide binding groove. This is likely to be due to a functional defect of the peptide-editor H2-M. Using Invariant-chain mutant mice and H2-M knock-out mice we confirmed that defective peptide exchange from MHC-II molecules hampered the anti-tumor responses and lead to enhanced tumor growth. These features of DC function, supported by RNA-Seq analysis, contribute to defective antigen presentation to CD4 T cells and may explain the dysfunction of DCs in tumor-bearing mice. Further analysis could allow us to “correct” these DC defects, thereby allowing CD4 T cell priming to provide the necessary help for antitumor CD8 T cells." @default.
- W4313405761 created "2023-01-06" @default.
- W4313405761 creator A5029421637 @default.
- W4313405761 creator A5061299469 @default.
- W4313405761 date "2022-05-01" @default.
- W4313405761 modified "2023-10-16" @default.
- W4313405761 title "Dysfunction of Dendritic Cells in Tumor-Draining Lymph Nodes" @default.
- W4313405761 doi "https://doi.org/10.4049/jimmunol.208.supp.61.05" @default.
- W4313405761 hasPublicationYear "2022" @default.
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