Effects of Hyperthermia and Hyperthermic Intraperitoneal Chemoperfusion on the Peritoneal and Tumor Immune Contexture

SIMPLE SUMMARY: Cancer that spreads to the lining of the abdomen, the peritoneum, is currently treated with heated chemotherapy and surgery. However, the effects of the high temperature on the cancer cells and the immune cells are still unclear. In this review, we summarize the available data to show that high temperatures may have both positive and negative effects, and that further study is necessary to distinguish these effects. ABSTRACT: Hyperthermia combined with intraperitoneal (IP) drug delivery is increasingly used in the treatment of peritoneal metastases (PM). Hyperthermia enhances tumor perfusion and increases drug penetration after IP delivery. The peritoneum is increasingly recognized as an immune-privileged organ with its own distinct immune microenvironment. Here, we review the immune landscape of the healthy peritoneal cavity and immune contexture of peritoneal metastases. Next, we review the potential benefits and unwanted tumor-promoting effects of hyperthermia and the associated heat shock response on the tumor immune microenvironment. We highlight the potential modulating effect of hyperthermia on the biomechanical properties of tumor tissue and the consequences for immune cell infiltration. Data from translational and clinical studies are reviewed. We conclude that (mild) hyperthermia and HIPEC have the potential to enhance antitumor immunity, but detailed further studies are required to distinguish beneficial from tumor-promoting effects.