Increasing Th1 phenotype in Th17 cells improves anti-tumor T cells function (VAC7P.1032)

Abstract

Abstract Immunotherapy of cancer is a promising approach for successful eradication of large and established tumor. While cytolytic CD8+ T cells have been extensively investigated and used for adoptive cell therapy (ACT), accumulating evidence indicates that CD4+ T helper (Th) cells including Th1 and Th17 subsets are also effective in tumor immunotherapy. Although Th1 cells possess key anti-tumor effector functions as IFNγhi, CD107ahi, T-bethi, Granzyme Bhi, but their poor persistence due to lack of stem-cell like characteristic effect long-term tumor control and reduce their potential in ACT. However, Th17 cells programmed ex vivo in TGFβ exhibit increased stem-cell like features and reduced effector function as compared to Th1 cells, which corelates to their increased persistence but reduced long-term tumor control. Herein we identified the ex vivo programming conditions that combine potent Th1 effector conditions with key stemness feature of Th17 to generate hybrid Th17/Th1 cells that exhibit improved control of murine melanoma (B16-F10) and human melanoma (624-MEL), as compared to Th1 or Th17 cells alone. The hybrid Th1/Th17 cells were less susceptible to activation induced cell death, exhibited increased persistence along with potent effector function, and have potential in future translational studies.