Of note, our work shows that dual-targeting IL-6 and CD40 plus ICIs completely eradicate GL261 tumors in all treated mice, suggesting that cocktail immunotherapy combining ICIs with neutralizing antibodies against IL-6 or IL-6 receptor, such as tocilizumab or sarilumab, and anti-CD40 agonist antibodies, such as APX005M, may act as an effective therapeutic approach for GBM, and possibly for other immunologically cold tumors, such as pancreatic, ovarian, and prostate cancers, which are characterized by a prominent infiltration of immunosuppressive Mφs. Here, IL6 is linked to glioblastoma.