Role of GM-CSF signaling in cell-based tumor immunization

Abstract

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cell-based vaccination in 2 tumor models. First, we vaccinated C57BL/6 mice lacking either GM-CSF, IL-5, or beta-common chain (βc), a receptor subunit essential for GM-CSF and IL-5 signaling, with melanoma cells engineered to produce GM-CSF. Tumor vaccination was effective in both GM-CSF−/− and IL-5−/− mice, showing that protective immunization is independent of both endogenous cytokines. However, all βc−/− animals developed tumor. Loss of tumor immunity in βc−/− mice does not reflect global impairment in cell-mediated immunity, as contact hypersensitivity reaction to haptens is unaltered. The importance of tumor cell–derived GM-CSF was highlighted by recruitment of dendritic cells at the vaccination site in wild-type, GM-CSF−/−, and IL-5−/− but not in βc−/− mice. In the second model, vaccination with unmodified RENCA cells showed similar results with efficient immunization in BALB/c wild-type and GM-CSF−/−, whereas all βc−/− animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through βc receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF–secreting tumor cells and a spontaneously immunogenic models.