Th17 cells play a role in multiple pathological scenarios. However, their functional phenotype, survival pattern and the underlying controlling mechanisms are poorly investigated in humans. This significantly hampers clinical application of targeting Th17 cells. Now we have studied Th17 cells in the pathological microenvironments of graft-versus-host disease, ulcerative colitis and cancer in humans. Th17 cells are increased in the chronic phase of these diseases. Th17 cells phenotypically resemble to terminally differentiated memory T cells, but are different from central memory, exhausted and senescent T cells. Despite their phenotypic markers of terminal differentiation, in vivo adoptive transfusing experiments demonstrate that Th17 cells mediate and promote long-term anti-tumor immunity. Furthermore, Th17 cells have important functional features including high capacity of proliferative self-renewal, potent persistence and apoptotic resistance in vivo, and the plasticity of converting into other types of T helper cells. These features are accompanied with relatively specific gene signature in Th17 cells including abundant anti-apoptotic genes. Moreover, we investigated the molecular mechanisms controlling their functional characters. We demonstrate that hypoxia inducible factor (HIF)1α and Notch collaboratively control key anti-apoptosis Bcl-2 family gene expression and function in Th17 cells. Altogether, the data indicate that human Th17 cells may be a long-lived proliferating effector memory T cell population with unique genetic and functional characters. These characters may be important determinants in Th17 cell biology. Targeting Th17-associated signaling pathway would be therapeutically meaningful for treating patients with autoimmune disease and advanced tumor.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3534. doi:1538-7445.AM2012-3534

©2012 American Association for Cancer Research
2012