Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment.

ABSTRACT: Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8⁺ effectors along tumor-stroma boundaries. The paradoxical accumulation of "poised" cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior. We find that, in human T cell-inflamed tumors, CD8⁺ T cells penetrate tumor nests, whereas cDC1s are confined within adjacent stroma that recurrently displays site-specific proteolysis of the matrix proteoglycan versican (VCAN), an essential organ-sculpting modification in development. VCAN is necessary, and its prot

SUBMITTER: Papadas A 

PROVIDER: S-EPMC9402878 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature