Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy

Macrophages are the most abundant and one of the most critical cells of tumor immunity. They provide a bridge between innate and adaptive immunity through releasing cytokines into the tumor microenvironment (TME). A number of interleukin (IL) cytokine family members is involved in shaping the final phenotype of macrophages toward either a classically-activated pro-inflammatory M1 state with anti-tumor activity or an alternatively-activated anti-inflammatory M2 state with pro-tumor activity. Shaping TME macrophages toward the M1 phenotype or recovering this phenotypic state may offer a promising therapeutic approach in patients with cancer. Here, we focus on the impact of macrophage-polarizing ILs on immune cells and IL-mediated cellular cross-interactions within the TME. The key aim of this review is to define therapeutic schedules for addressing ILs in cancer immunotherapy based on their multi-directional impacts in such a milieu. Gathering more knowledge on this area is also important for defining adverse effects related to cytokine therapy and addressing them for reinforcing the efficacy of immunotherapy against cancer.