Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma

Our plain-English summary of Chemoimmunotherapy: an emerging strategy for the treatment of malignant mesothelioma, by M.J. McCoy, A.K. Nowak, R.A. Lake (Tissue Antigens, 2009).

The study

• Authors: M.J. McCoy, A.K. Nowak, R.A. Lake
• Journal: Tissue Antigens
• Published: 2009;74(1):1-10
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Whether the immune system can recognize malignant and premalignant cells and eliminate them to prevent the development of cancer is still a matter of open debate, but in our view, the balance of evidence favours this concept. Nonetheless, the International Agency for Research on Cancer has now predicted that cancer will overtake heart disease as the leading cause of death worldwide by 2010, showing that this protective mechanism often fails. Malignant mesothelioma has traditionally been considered a relatively non-immunogenic cancer. However, mesothelioma cells do express a set of well-defined tumour antigens that have been shown to engage with the host immune system. Mesothelioma should therefore be considered a target for immunotherapy. A variety of anticancer immunotherapies have been investigated in mesothelioma and in other malignancies, although these have been largely ineffective when used in isolation. Over recent years, there has been increasing interest in the possibility of combining immunotherapy with chemotherapy in the fight against cancer. Here, we discuss the rationale behind combining these two, long considered antagonistic, treatment options in the context of malignant mesothelioma.

In plain English

This 2009 article was a review, not an original study. The authors discussed the reasoning for combining chemotherapy with immunotherapy (treatments that harness the immune system) for malignant mesothelioma. They noted that standard chemotherapy with cisplatin and pemetrexed gave a modest survival benefit, with median survival still only 9–12 months from diagnosis. They reviewed evidence that mesothelioma cells carry tumour antigens, such as mesothelin, and stated that immunotherapies used alone had, on the whole, been disappointing in patients. Studies they cited reported two findings. In mice with mesothelioma, gemcitabine followed by an immune-stimulating antibody (FGK45) produced long-term cures in up to 80% of animals. In patients with malignant pleural mesothelioma who received chemotherapy before surgery called extrapleural pneumonectomy, high levels of CD8 T cells in the tumour after chemotherapy predicted delayed recurrence and improved survival. The authors noted that few studies had linked such immune changes to clinical response in patients. They concluded that combining standard chemotherapy with immunotherapy may be the way forward, with careful drug selection, dosing and scheduling.

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: Review article (narrative review of published laboratory, animal and clinical research, with some of the authors' own unpublished data)
• Who was studied: No study population of its own. The authors reviewed published research on immune responses to mesothelioma and on immunotherapies and chemotherapy, mainly in mouse models, with some clinical trials in patients.
• Exposure: Not a study of asbestos exposure. Asbestos was mentioned only as background, as the major cause of mesothelioma. The treatments reviewed were chemotherapy drugs (including cisplatin, pemetrexed, gemcitabine, cyclophosphamide and doxorubicin) and immunotherapies (including type I interferons, CD40 activation, regulatory T cell depletion, IL-2 and mesothelin-targeted therapy).
• Main results:
  • The authors reported that for patients with advanced mesothelioma treated with palliative cisplatin and pemetrexed, median survival was still only 9–12 months from diagnosis.
  • The authors stated that immunotherapies showing promise in preclinical studies had, on the whole, been disappointing when used alone in patients.
  • A cited mouse study of mesothelioma found that gemcitabine combined with the immune-stimulating antibody FGK45 produced long-term cures in up to 80% of animals. The combination worked only when FGK45 followed gemcitabine.
  • A cited study (Anraku et al.) looked at patients with malignant pleural mesothelioma who had received induction chemotherapy (cisplatin with pemetrexed, or cisplatin with vinorelbine) before extrapleural pneumonectomy. In these patients, high levels of CD8 tumour-infiltrating T cells after chemotherapy were an independent predictor of delayed recurrence and improved survival.
  • In cited work on patients with advanced metastatic cancer, cyclophosphamide at 100 mg/day selectively depleted regulatory T cells, while 200 mg/day depleted all lymphocyte subsets.
  • In the authors' own unpublished data from a mouse mesothelioma model, doxorubicin was less dependent on a fully functional immune system than pemetrexed or gemcitabine.
• The authors' conclusion: The authors proposed that combining current standard chemotherapy with immunotherapy may be the way forward in treating mesothelioma. They stated that careful drug selection, dosing and scheduling will be needed.
• Limitations the authors state:
  • The authors noted that few studies had examined whether chemotherapy-induced immune changes relate to clinical response in cancer patients.
  • The authors noted that CD40-activating strategies had not yet been tested in mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Immunotherapy, Chemotherapy.

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• Modulating Immunosuppression in the Intrapleural Space of Malignant Pleural Mesothelioma and Predictive Biomarkers to Guide Treatment Decisions — R.M. Wong (2016)
• Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification — L. Urso, M. Silic-Benussi, et al. (2021)
• Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma — S.G. Gray (2021)
• Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases — E. McGehee, D.E. Gerber, et al. (2019)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)

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