Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Our plain-English summary of Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach, by D. Lisini, S. Lettieri, S. Nava, et al (International Journal of Molecular Sciences, 2021).

The study

• Authors: D. Lisini, S. Lettieri, S. Nava, G. Accordino, S. Frigerio, C. Bortolotto, A. Lancia, A.R. Filippi, F. Agustoni, L. Pandolfi, D. Piloni, P. Comoli, A.G. Corsico, G.M. Stella
• Journal: International Journal of Molecular Sciences
• Published: 2021;22(16)
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This article was a review. The authors summarized published research on treatments delivered directly into the chest cavity or tumor (local therapies) for malignant pleural mesothelioma (MPM), which they described as an asbestos-related cancer. They also discussed how these treatments interact with the tissue around the tumor. Topics included drug-carrying nanoparticles such as liposomes, dendritic cell vaccines, CAR-T cells, mesenchymal stromal cells, implanted biomaterials and imaging methods. Among the studies described, mouse experiments reported that pemetrexed carried in liposomes and injected into the pleural cavity suppressed tumor growth more than free pemetrexed. A Phase I trial of dendritic cells loaded with donor tumor material (MesoCancerVa) recorded no dose-limiting toxicities and a median progression-free survival of 8.8 months. The authors noted that a certain imaging approach had not yet been applied to MPM. The authors concluded that, although few data were yet available, the features of MPM made it potentially suited to local therapies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory, animal and clinical studies on local therapies for malignant pleural mesothelioma
• Who was studied: The review covered published studies (cell experiments, mouse models and early clinical trials) of local treatments for malignant pleural mesothelioma. A figure also showed two scans from one patient to illustrate imaging methods.
• Exposure: Not a study of asbestos exposure. The authors described MPM as an asbestos-related cancer and asbestos-driven inflammation as shaping the tumor's surrounding tissue. No fiber types, jobs or doses were studied. The subject of the review was local treatments.
• Main results:
  • Reported from another study (Ando et al.): in an orthotopic mesothelioma mouse model, pemetrexed loaded into liposomes and injected into the pleural cavity suppressed tumor growth more than free pemetrexed.
  • Reported from another study (Marazioti et al., mice): small or PEGylated liposomes injected into the pleural cavity were retained longer. The pattern of clearance was the same in normal mice and MPM-bearing mice.
  • Reported from another study (Schulz et al., animals): after surgical resection, only paclitaxel carried in expansile nanoparticles significantly extended survival, compared with surgery alone or surgery plus free paclitaxel.
  • Reported from other studies: early MPM approaches using dendritic cells loaded with the patient's own tumor lysate showed persistent clinical responses, with overall survival up to a maximum of 66 months.
  • Reported from the Phase I MesoCancerVa trial of dendritic cells loaded with allogeneic tumor lysate: no dose-limiting toxicities were recorded. Median progression-free survival was 8.8 months, and median overall survival was not reached at a median follow-up of 22.8 months.
  • The authors noted that radiomics (computer analysis of medical images) had not yet been applied to MPM to assess tumor-infiltrating CD8 cells or responses to anti-PD-1 or anti-PD-L1 immunotherapy.
• The authors' conclusion: The authors concluded that, although few data were yet available on MPM, its specific disease features made it potentially susceptible to local therapeutic approaches. They said clinical validation studies were needed to identify which patients are likely to respond.
• Limitations the authors state:
  • The authors stated that a detailed description of the tissue surrounding MPM tumors was beyond the scope of the review.
  • The authors noted that the nanoparticle field is relatively new.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Mesothelium, Asbestos Exposure, Immunotherapy, Chemotherapy.

Related studies

• Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design — G.M. Stella, D. Lisini, et al. (2024)
• A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy — Y. Watanabe, T. Kojima, et al. (2010)
• Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients — K. Suzuki, K. Kadota, et al. (2011)
• Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies — D.A. Mahvi, R. Liu, et al. (2018)
• Local and systemic therapies for malignant pleural mesothelioma — D. Gomez, A.S. Tsao (2014)
• Emerging translational therapies for mesothelioma — H.I. Pass, B.W. Robinson, et al. (1999)

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