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Differential roles of TSLP and IL-33 in regulation of Treg cells in progression of colorectal cancer

ABSTRACT: Recruitment of regulatory T cells (Tregs) to tumors is a hallmark of cancer progression. However, the role of epithelial cell-derived cytokines in regulation of Treg cells in colorectal cancers is not fully understood. We found a subset of Tregs co-expressing the receptors for thymic stromal lymphopoietin (TSLP) and IL-33 (TSLPR+ST2+ Tregs) was increased in colorectal tumors in humans and mice. This Treg subset expressed high levels of CTLA-4 and PD-1, and TSLPR signaling regulated the expression of CTLA-4 and number of TSLPR+ST2+ Tregs. Treg-specfic deletion of TSLPR resulted in a reduction in tumor number and size, with concomitant increase of Th1 cells in tumors. Similarly, blockade of TSLP effectively inhibited progression of colorectal tumors. On the other hand, TSLPR-ST2+ Tregs highly express Tgfb1 and Pdcd,1 which have been shown to suppress CD8+ T cell immune responses. Collectively, TSLP and IL-33 differentially regulate subsets of Tregs in the progression of colorectal tumor. These data suggest that TSLPR+ST2+ Treg cells are potentially a biomarker, and a therapeutic target for CRC.

ORGANISM(S): Mus musculus

PROVIDER: GSE173124 | GEO | 2021/12/22

REPOSITORIES: GEO

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