Kao et al. (4) showed that patients with solid tumors receiving ICI had elevations in cytokines, including IL-6, and were at risk for irAEs. Importantly, IL-6 correlated with decreased ORR and worse mortality (4). In the tumor microenvironment (TME), IL-6 increases the quantity of Tregs and MDSCs, promotes T cell exhaustion, negatively regulates effector T cells, and modulates NK cells and dendritic cells. IL-6 also increases the production of STAT and VEGF in tumor cells with tumor proliferating effects. Systemically, IL-6 promotes differentiation of activated T cells and increases inflammation and tissue remodeling via tissue-resident monocytes and stromal cells. Notably, tumor cells and cells within the tumor microenvironment, including tumor-infiltrating lymphocytes and stromal cells, express IL-6 receptors. Tissue and circulating immune cells involved with irAEs also express IL-6 receptors. Targeting the IL-6 receptor with blocking antibodies in solid tumors treated with ICI may improve the response to treatment while decreasing the risk for irAEs.