GM-CSF promotes antitumor immunity by inducing Th9 cell responses

Abstract

GM-CSF as an adjuvant has been shown to promote anti-tumor immunity in mice andhumans; however, theunderlying mechanism ofGM-CSF-induced antitumorimmunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating theCOX2-PGE2 pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells in vitro and in vivo. GM-CSF-activated monocyte-derived dendritic cells converted tumor-specific naive Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.