Figure 1.

Hyperthermia creates a type I-like tumor microenvironment, and the multifaceted mechanisms make hyperthermia a potent immune checkpoint inhibitor sensitizer. (1) Hyperthermia increases the tumor mutation burden/neoantigen and promotes immunogenic cell death. These two aspects promote DC activation maturation and thus transform the immunosuppressive microenvironment by inhibiting Treg cells and promoting tumor-infiltrating lymphocyte recruitment. (2) Hyperthermia can directly promote DC and T cell maturation. (3) Exosomes extracted from heat-stressed tumor cells (HS-TEX) act as a cancer vaccine to activate DCs and promote cells to secrete IL-6 to transform the immunosuppressive TME (marked with dotted lines) (4) Hyperthermia can upregulate PD-L1 expression in an elevated temperature.