PT  - JOURNAL ARTICLE
AU  - Nicholas Borcherding
AU  - Kawther K. Ahmed
AU  - Andrew P. Voigt
AU  - Ajaykumar Vishwakarma
AU  - Ryan Kolb
AU  - Paige Kluz
AU  - Gaurav Pandey
AU  - Katherine N. Gibson-Corley
AU  - Julia Klesney-Tait
AU  - Yuwen Zhu
AU  - Jinglu Lu
AU  - Jinsong Lu
AU  - Xian Huang
AU  - Jinke Cheng
AU  - Song Guo Zheng
AU  - Xuefeng Wu
AU  - Yousef Zakharia
AU  - Weizhou Zhang
TI  - Transcriptional heterogeneity in cancer-associated regulatory T cells is predictive of survival
AID  - 10.1101/478628
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 478628
4099  - http://biorxiv.org/content/early/2018/11/26/478628.short
4100  - http://biorxiv.org/content/early/2018/11/26/478628.full
AB  - Regulatory T cells (Tregs) are a population of T cells that exert a suppressive effect on a variety of immune cells and non-immune cells. The suppressive effects of Tregs are detrimental to anti-tumor immunity. Recent investigations into cancer-associated Tregs have identified common expression patterns for tumor-infiltration, however the functional heterogeneity in tumor-infiltrating (TI) Treg is largely unknown. We performed single-cell sequencing on immune cells derived from renal clear cell carcinoma (ccRCC) patients, isolating 160 peripheral-blood (PB) Tregs and 574 TI Tregs. We identified distinct transcriptional TI Treg cell fates, with a suppressive subset expressing CD177. We demonstrate CD177+ TI-Tregs have preferential suppressive effects in vivo and ex vivo. Gene signatures derived the CD177+ Treg subset had superior ability to predict survival in ccRCC and seven other cancer types. Further investigation into the development and regulation of TI-Treg heterogeneity will be vital to the application of tumor immunotherapies that possess minimal side effects.