How Hyperthermic Intrathoracic Chemotherapy Remodels the Immune Microenvironment in Pleural Mesothelioma

New research suggests that hyperthermic intrathoracic chemotherapy (HITOC) plus immune checkpoint inhibitors (ICI) should be evaluated in a clinical trial for the treatment of pleural mesothelioma, according to a recent study published in Cancer Immunology Research.

The study was conducted by a team of researchers from Switzerland. They aimed to evaluate the effect of HITOC, “a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs.”

It was important to perform this research because of the limited treatment options and high morbidity of pleural mesothelioma. The investigators explained that in first-line therapy, “dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy.”

However, although ICIs have recently improved pleural mesothelioma management, “only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required.”

The researchers developed a murine pleural mesothelioma model of HITOC to explore the impact of HITOC on the disease. Through a mechanism involving cytotoxic immune response, the model showed that HITOC “significantly improved” both animal survival and tumor control.

Furthermore, immune checkpoint expression was enhanced by HITOC through T lymphocytes and dual PD-1 and CTLA-4 inhibition. This development led to increased improvement in animal survival within the model.

The investigators also analyzed samples from patients with peritoneal mesothelioma, which were treated by pressurized intraperitoneal aerosol chemotherapy. According to the results, the treated samples showed “similar immunomodulation.”

The researchers concluded that by promoting T-cell infiltration of tumors, HITOC was able to remodel the tumor immune microenvironment of pleural mesothelioma and recommended the combination of HITOC and ICIs be further researched in the “context of a clinical trial.”

Reference

Hao Y, Gkasti A, Managh AJ, et al. Hyperthermic Intrathoracic Chemotherapy Modulates the Immune Microenvironment of Pleural Mesothelioma and Improves the Impact of Dual Immune Checkpoint Inhibition. Cancer Immunol Res. 2025;13(2):185-199. doi:10.1158/2326-6066.CIR-24-0245