Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop.

ABSTRACT: Foxp3⁺ T regulatory (Treg) cells promote immunological tumor tolerance, but how their immune-suppressive function is regulated in the tumor microenvironment (TME) remains unknown. Here, we used intravital microscopy to characterize the cellular interactions that provide tumor-infiltrating Treg cells with critical activation signals. We found that the polyclonal Treg cell repertoire is pre-enriched to recognize antigens presented by tumor-associated conventional dendritic cells (cDCs). Unstable cDC contacts sufficed to sustain Treg cell function, whereas T helper cells were activated during stable interactions. Contact instability resulted from CTLA-4-dependent downregulation of co-stimulatory B7-family proteins on cDCs, mediated by Treg cells themselves. CTLA-4-blockade triggere

SUBMITTER: Marangoni F 

PROVIDER: S-EPMC8664158 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature