[Hyperthermia Enhances Antitumor Effects of Immune Checkpoint Inhibitors and Immune Cell Therapy]

Hyperthermia is known to enhance the effects of radiotherapy and chemotherapy. We have previously shown that hyperthermia also enhances the effects of molecular targeted therapy, immune cell therapy, and immune checkpoint inhibitors (ICI). Here, we present the recent clinical data and research results that suggest the mechanism of enhancement. Clinical data: We treated 3,419 advanced or recurrent cancer patients between June 2005 to December 2023. The effective rate (CR+PR+long term SD)was 19.7%. The effective rate of 2,329 patients treated with dendritic cells was 25.4%. The effective rate of 140 patients treated with combined dendritic cell therapy and ICI was high at 56.4%, and increased from 40.0 to 57.7% by the addition of hyperthermia. Clinical tissue: Hyperthermia promoted immune cell infiltration and enhanced MHC-class Ⅰ and PD-L1. Animal experiments: We have previously reported that hyperthermia promotes immune cell infiltration and increases MHC-class Ⅰ and PD-L1. We showed that hyperthermia increased p-STAT1 and IRF1 followed by PD-L1 expression. This study suggested that hyperthermia increased ICI through immune cell infiltration and expression of p-STAT1 and IRF1 pathways.