GSE173124
Differential roles of TSLP and IL-33 in regulation of Treg cells in progression of colorectal cancer
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. Overall design: 33 samples total. 4 mice with tumors, 5 without. 4 T-cell populations defined by ST2 and TSLP positivity for 8 mice, 1 naive T-cell population for 1 mouse