Immunotherapy for malignant pleural mesothelioma. Current status and future prospects

Our plain-English summary of Immunotherapy for malignant pleural mesothelioma. Current status and future prospects, by R.M. Wong, I. Ianculescu, S. Sharma, et al (American Journal of Respiratory Cell and Molecular Biology, 2014).

The study

• Authors: R.M. Wong, I. Ianculescu, S. Sharma, D.L. Gage, O.M. Olevsky, S. Kotova, M.N. Kostic, W.S. Grundfest, D. Hou, R.B. Cameron
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2014;50(5):870-5
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and/or systemic immunosuppressive factors, thus creating a host environment more amenable to immunotherapy. This article reviews the immunotherapeutic approaches being evaluated in patients with MPM and discusses how immunotherapy might be rationally combined with conventional tumor cytoreductive therapies for this disease.

In plain English

This article was a review, not an original study. The authors summarized published and ongoing research on immunotherapy (treatments that work through the immune system) for malignant pleural mesothelioma, a rare cancer of the pleura, the lining around the lungs. They noted that the only treatment shown in randomized phase III trials to prolong survival was pemetrexed/cisplatin chemotherapy, which extended median survival by 2.8 months. Among the studies they cited, Astoul and colleagues reported responses to IL-2 given into the chest cavity in 12 of 22 patients, all with early-stage epithelioid disease. A tremelimumab trial by Calabrò and colleagues, in 29 patients with chemotherapy-resistant advanced mesothelioma (28 pleural, 1 peritoneal), reported tumor responses in 2 patients and disease stabilization in nine (31%), all with epithelioid histology. The authors also described vaccines, engineered T cells tested in mice, and mouse studies that combined immunotherapy with radiation, chemotherapy or surgery. The authors concluded that responses to immunotherapy, though infrequent, might be improved by overcoming immune suppression. They added that combined treatments still needed careful evaluation before clinical trials. The review did not study asbestos exposure.

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 (translational review) of immunotherapy research in malignant pleural mesothelioma
• Who was studied: Published clinical trials and registered ongoing trials in patients with malignant pleural mesothelioma, plus laboratory and mouse (murine) studies. The number of studies reviewed and the search method are not stated.
• Exposure: Not an asbestos exposure study. The treatments reviewed were immunotherapies (cytokines such as IL-2 and interferons, mesothelin-targeted antibodies, vaccines, CAR T cells, immune checkpoint blockade) and their combination with radiation, chemotherapy and surgery. Asbestos is mentioned only in background: the disease can occur in shipyard workers, teachers and close relatives of those who worked with asbestos.
• Main results:
  • Background stated by the authors, citing a phase III trial: pemetrexed/cisplatin was the only treatment shown in randomized phase III trials to prolong overall survival, extending median survival by 2.8 months.
  • Cited study (Astoul and colleagues): intrapleural IL-2 produced objective responses in 12 of 22 (54%) patients with malignant pleural mesothelioma. All responders had early-stage epithelioid histology.
  • Cited study (Calabrò and colleagues): in 29 patients with chemotherapy-resistant advanced mesothelioma (28 pleural, 1 peritoneal) given tremelimumab, objective responses occurred in 2 of 29 and disease stabilization in nine (31%), all with epithelioid histology.
  • Cited study (Calabrò and colleagues): overall survival in the tremelimumab trial was 48% at 1 year and 37% at 2 years.
  • Cited study (Hassan and colleagues): SS1P antimesothelin immunotoxin combined with pentostatin/cyclophosphamide produced tumor shrinkage in 3 of 10 patients and disease stabilization in another 3 of 10.
  • Cited mouse study (Fridlender and colleagues): interferon-alpha immunogene therapy given into the tumor, followed by cisplatin plus gemcitabine, produced complete regression of established mesothelioma tumors in 13 of 15 treated mice.
• The authors' conclusion: The authors concluded that clinical responses of malignant pleural mesothelioma to immunotherapy, although infrequent, might be improved by overcoming immune suppression within tumors and/or throughout the body, for example with radiation, chemotherapy or surgery.
• Limitations the authors state:
  • The authors stated that the choice, dosage and timing of each part of the combined regimens tested in mice still needed careful evaluation before clinical trials are planned.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Pleura, Macrophage, Cytoreductive Surgery, Chemotherapy.

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