ICOS signaling in CD8+ CTL contributes to the antitumor efficacy (P2122)

Abstract

Abstract The expression of Inducible costimulator (ICOS) on CD8+ CTL and its role in antitumor immunity remains largely unknown. To address this issue, we crossed ICOS-deficient mice with pmel-1 transgenic mice to generate pmel1/ICOS-/- mice. The loss of ICOS in pmel-1CD8+ CTL cells did not affect the expression of other T cell activation markers (e.g. CD25 and CD69) but led to a significant decrease in IFN-gamma production and killing of target tumor cells. Similarly, adoptive transfer of pmel-1 cells into ICOS-ligand knockout mice showed impaired cell proliferation and decreased expression of IFN-gamma and CD107a. Most importantly, when activated ICOS- / - pmel-1 cells were adoptively tranfered into tumor-bearing mice they displayed poor proliferation and diminished antitumor activity as compared to ICOS-intact pmel-1 cells. These results provide direct evidence for the important role of ICOS in CD8+ CTL mediated antitumor immunity and have implications in the development of novel immunotherapy for cancer by manupilation of ICOS pathway.