Tumor-associated Tregs mediate translational regulation in effector T cells 3350

Description Regulatory T cell (Treg) is a hallmark of progression of tumor. We presented that TSLP receptor-expressing Tregs (TSLPR+ Tregs) uniquely emerged in colorectal tumors in both humans and mice, published in Sci Transl Med in 2022. Recently, we identified the novel molecular mechanism of Treg-mediated suppression against effector T helper cells (Teffs). Transcriptomic and translatome analysis showed that mRNAs encoding for ribosome machinery in Teffs were negatively regulated by Tregs through inhibiting mTORC1 signaling by IL-10 and TGF-b, also leading to reduction of global protein synthesis in Teffs. TSLPR+ Tregs induce significantly higher levels of reduction of protein synthesis in Teffs compared to other Treg subsets. Intriguingly, TSLP signaling on Tregs induces the exclusive expression of Mef2C, a transcription factor, on this Treg, which controls the number and functions of this Treg. Blockage of TSLP signaling dampens TSLPR+ Treg-mediated suppression of Teffs in colorectal cancer mouse models, resulting in mitigation of progression of tumors. These data suggest that TSLP plays a critical role in Treg-mediated translational regulation in Teffs. Funding Sources Washington Research Foundation, Andy Hill CARE Fund Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)