Abstract
Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.
Highlights
This article is an open access articleMalignant pleural mesothelioma (MPM) is a fatal asbestos-related malignancy which originates from the mesothelial layer which coat the pleural space
Malignant Pleural Mesothelioma (MPM) has been listed an orphan disease by the European Union (EU). The latter assures that the disease is enclosed into the European Reference Network (ERN) for the lung that is dedicated to rare respiratory diseases, which has the main aims to: facilitate improvements in access to diagnosis and delivery of high quality, accessible and cost-effective healthcare for people living with rare diseases, and act as focal points for medical training and research, information dissemination and evaluation, especially for rare diseases
The characterization of the immune micro-environment has been significantly associated with patient prognosis [25], being those infiltrates featuring by low CD4POS lymphocytes and high CD8POS and high PD-L1 expression associated with poor patient survival [26,27,28]
Summary
Malignant pleural mesothelioma (MPM) is a fatal asbestos-related malignancy which originates from the mesothelial layer which coat the pleural space. Among the most promising therapeutic strategies that are under investigation, there is the local delivery of biologic and chemical agents These approaches exploit the typical progression pattern of MPM which is most often localized, whereas distant spreading rarely occurs. Several strategies are under development encompassing surgery, ionizing radiation, biologic agents and cells and nanoparticles This present work aims at summarizing the novel approaches. Sci. 2021, 22, 9014 for local therapy in MPM, with a primary focus on the rationale of this approach, which assures a closed contact with the immune/inflammatory and vascular processes which characterize the MPM stroma From this perspective, advanced cell therapies, which aim at increasing the number of effector cells against the tumor, might play a substantial role which is favored by their dynamic interaction with tumor stroma
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