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

Borcherding, N.; Ahmed, K. K.; Voigt, A. P.; Vishwakarma, A.; Kolb, R.; Kluz, P.; Pandey, G.; Gibson-Corley, K. N.; Klesney-Tait, J.; Zhu, Y.; Lu, J.; Huang, X.; Cheng, J.; Zheng, S. G.; Wu, X.; Zakharia, Y.; Zhang, W.

doi:10.1101/478628

bioRxiv · 10.1101/478628

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

Borcherding, N.·Ahmed, K. K.·Voigt, A. P.·Vishwakarma, A.·Kolb, R.·Kluz, P.·Pandey, G.·Gibson-Corley, K. N.·Klesney-Tait, J.·Zhu, Y.·Lu, J.·Huang, X.·Cheng, J.·Zheng, S. G.·Wu, X.·Zakharia, Y.·Zhang, W.

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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.

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Borcherding, N., Ahmed, K. K., Voigt, A. P., Vishwakarma, A., Kolb, R., Kluz, P., Pandey, G., Gibson-Corley, K. N., Klesney-Tait, J., Zhu, Y., Lu, J., Huang, X., Cheng, J., Zheng, S. G., Wu, X., Zakharia, Y., Zhang, W.. 2018-11-26. Transcriptional heterogeneity in cancer-associated regulatory T cells is predictive of survival.. https://doi.org/10.1101/478628

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