Inflammasomes/IL-1 pathways in myeloid cells modulate PD-1/PD-L1 checkpoint molecules

Abstract

Abstract The inflammatory microenvironment is not only critical for tumor growth and progression, but also associated with immunosuppression. Expression of immune checkpoint molecules, such as PD-L1, in tumor cells and innate immune cells has been linked to diminished anti-tumor response. However, the connection between inflammation and expression of checkpoint molecules in myeloid cells and tumor cells is poorly characterized. Our recent studies have demonstrated that the inflammasome and IL-1β pathway plays a critical role in promoting tumor growth and metastasis. Our data show that inflammasome activation promoted the infiltration of myeloid cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, into tumor microenvironments. Interestingly, we found that inflammasome/IL-1 pathways induced expression of immune checkpoint molecule PD-L1 on infiltrated myeloid cells and tumor cells. Furthermore, blocking IL-1R with IL-1R antagonist (IL-Ra) or anti-IL-1R antibody inhibits tumor growth and metastasis accompanied by decreased accumulation of myeloid cells and expression of the PD-L1 molecule. Together, our results demonstrate that inflammasomes/IL-1 pathways promote infiltration of myeloid cells and expression of PD-L1, contributing to tumor immune evasion and tumor progression.