Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects

Abstract

Malignant mesothelioma is a rare and aggressive cancer that develops in the thin layer surrounding the mesothelium and is mainly caused by asbestos exposure. Despite improvements in patient prognosis with conventional cancer treatments, such as surgery, chemotherapy, and radiotherapy, there are still no curative treatment modalities for advanced disease. In recent years, new therapeutic avenues have been explored. Improved understanding of the mechanisms underlying the dynamic tumor interaction with the immune system has led to the development of immunotherapeutic approaches. Numerous recent clinical trials have shown a desire to develop more effective treatments that can be used to fight against the disease. Immune checkpoint inhibitors, oncolytic adenoviruses, and their combination represent a promising strategy that can be used to synergistically overcome immunosuppression in the mesothelioma tumor microenvironment. This review provides a synthesized overview of the current state of knowledge on new therapeutic options for mesothelioma with a focus on the results of clinical trials conducted in the field.

Keywords: combination therapy; immune checkpoint inhibitors; immunotherapy; mesothelioma; oncolytic adenoviruses.

Figure 1

Schematic overview of future perspectives in mesothelioma immunotherapy. Novel approaches under investigation aimed at stimulating the immune system in the treatment of mesothelioma can be divided into different classes. Oncolytic virotherapy, alone or in combination with ICIs, can selectively kill cancer cells as well as boosting a strong antitumor immune reaction. Cancer vaccines are classified into cell-based vaccines with the purpose of activating effector T cells, and antigen peptides preparation (WT1-analogue vaccine) which selectively stimulates the immune system. Adoptive T cell therapy presenting anti-mesothelin CAR are mainly used for their ability to specifically recognize exposed tumor antigens. Immunosuppressive factors inhibitors such as VISTA, LAG-3 and TIM-3 inhibitors can block these molecules, known for their involvement into the tumor immune silencing. Immunostimulatory agents as OX40/OX40L and TLR9 agonists can boost a selectively immune reaction towards the tumor microenvironment. Created with BioRender.com.