Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation
Significance Inflammation and immunosuppression are dominant features of cancer progression. In the tumor microenvironment, macrophages produce interleukin-1β (IL-1β), which subsequently recruits myeloid cells from the bone marrow. In mice deficient in IL-1β or in wild-type mice treated with anti–IL-1β Abs, implanted breast cancer tumors regress. Regression is due to decreased tumor-related immunosuppression, meditated mainly by macrophages, and increased antitumor immunity, mediated by elevated dendritic cell function and activated cytotoxic CD8 lymphocytes. Although anti–PD-1 reduces tumor growth, the combination of anti–IL-1β plus anti–PD-1 abrogated the tumors completely. These observations support clinical trials of blocking IL-1β in cancer and that anti–IL-1β is a checkpoint inhibitor.