An important step forward in the fight against pleural mesothelioma, an aggressive form of cancer that affects the lining of the lungs, comes from an international study published in the prestigious scientific journal Nature Genetics. The paper, titled Tumor DNA Methylation Subtypes Predict Immunotherapy Outcomes in Pleural Mesothelioma Patients in the NIBIT-EPI-MESO Study, was coordinated by the Biogem Computational Biology laboratory, in collaboration with the University of Siena, the University of Ferrara, and several other Italian and international research centers.
The study analyzed the role of DNA methylation, an epigenetic mechanism that regulates gene activity without altering its sequence, and its impact on the response to immunotherapy in patients with pleural mesothelioma.
Through an advanced analysis of tumor samples from 91 patients treated with immunotherapy, the authors discovered that specific tumor "epigenetic profiles" are closely linked to both the likelihood of response to treatment and the patient survival.
Specifically, the results show that DNA methylation can directly influence the immune system's response to tumors, regulating genes involved in inflammation, the tumor's ability to be recognized by the immune system, and the attraction of immune cells to the diseased area. This means that some patients, based on the molecular characteristics of their tumor, may benefit more from the immunotherapy drugs currently available, such as immune checkpoint inhibitors anti-PD-1 and anti-CTLA-4, while others may achieve more limited results.
Another significant result is the development of a predictive model capable of estimating, through DNA methylation analysis, the likelihood of a patient responding positively to immunotherapy. This tool could contribute to increasingly personalized and targeted treatments in the future.
The research reported in this paper is part of an activity started a while ago by the same Biogem group in the field of metastatic melanoma, reinforcing the idea that epigenetic characteristics of tumors play a crucial role in determining the efficacy of immunological therapies.
Overall, the study opens new perspectives for the development of therapeutic strategies combining immunotherapy and epigenetics, with the aim of making tumors more vulnerable to the immune system's action and concretely improving the treatment options for patients.
For more information: https://www.nature.com/articles/s41588-026-02580-4
