Th17 cells have stem cell-like features and promote long-term immunity

Memory T cells are one of the most effective components of anti-tumor immunity. However, limited studies on cancer patients have not addressed the phenotypic, genetic and functional heterogeneity of memory T-cell subsets in the human cancer environments. Human IL-17(+)CD4(+) (Th17) cells are confined to memory T-cell compartment with CD45RO(+)CD62L(-)CCR7(-) phenotype and are enriched in CD49(+)CCR6(+) population. Th17 cells do not express PD-1, FoxP3, KLRG-1, CD57 and IL-10, making them unlikely candidates for being functionally exhausted PD-1(+) T cells or suppressive Foxp3(+) or IL-10(+) T cells or senescent CD28(-)CD57(+)KLRG-1(+) T cells. However, Th17 cells express high levels of CD95 and moderate levels of CD27. Th17 cells phenotypically resemble terminally differentiated memory T cells. Interestingly, Th17 cells possess polyfunctional cytokine profile, and have stem cell-like features. Th17 stemness may be partially controlled by signaling pathways of hypoxia inducible factor HIF1α, Notch and Bcl. The stem cell-like character of Th17 cells is an important decisive factor for Th17 cell biology.