DOI: 10.1101/478628Nov 26, 2018Paper

Transcriptional heterogeneity in cancer-associated regulatory T cells is predictive of survival.

BioRxiv : the Preprint Server for Biology
Nicholas BorcherdingWeizhou Zhang

Abstract

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.

Related Concepts

Malignant Neoplasms
Renal Cell Carcinoma
Immunotherapy
Neoplasms
T-Lymphocyte
Regulatory T-Lymphocytes
Transcription, Genetic
Lymphocytes, Tumor-Infiltrating
Peripheral Blood
Conventional (Clear Cell) Renal Cell Carcinoma

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