New roads open up for implementing immunotherapy in mesothelioma

Our plain-English summary of New roads open up for implementing immunotherapy in mesothelioma, by R. Cornelissen, M.E. Heuvers, A.P. Maat, et al (Clinical & Developmental Immunology, 2012).

The study

• Authors: R. Cornelissen, M.E. Heuvers, A.P. Maat, R.W. Hendriks, H.C. Hoogsteden, J.G. Aerts, J.P. Hegmans
• Journal: Clinical & Developmental Immunology
• Published: 2012;2012:927240
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems.

In plain English

This article was a review of immunotherapy for malignant mesothelioma. It reported no new data of its own and did not discuss asbestos or any other fiber exposure. The authors noted that chemotherapy was the only evidence-based treatment for mesothelioma patients in good clinical condition, increasing median survival by only 2 months. They described how tumours escape the immune system, focusing on three suppressive cell types: myeloid-derived suppressor cells, tumour-associated macrophages and regulatory T cells. They summarised earlier trials. One was another group's vaccine trial in 22 patients, in which 32% developed at least one type of immune response but no major tumour regressions were seen. Another was their own group's dendritic-cell vaccine trial, which was well tolerated and induced an immune reaction. They also described mouse experiments with drugs such as celecoxib and zoledronic acid. The authors concluded that combination therapy targeting several cell types will probably be necessary. They suggested that measuring tumour shrinkage on CT scans may not capture the benefit of immunotherapy.

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
• Who was studied: No study population of its own; a review of published laboratory, animal and clinical research on immune cells and immunotherapy in malignant mesothelioma
• Main results:
  • The authors stated that chemotherapy was the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months.
  • The review identified myeloid-derived suppressor cells, tumour-associated macrophages and regulatory T cells as the main cells that hamper the immune response against the tumour.
  • The review described another research group's trial of an autologous tumour cell vaccine given with GM-CSF. Twenty-two patients were enrolled and 32% developed at least one type of anti-mesothelioma immune response, but no major tumour regressions were observed.
  • The review described the authors' group's earlier first clinical trial of tumour lysate-loaded dendritic cells in mesothelioma patients. The vaccination was well tolerated and induced an immune reaction.
  • In the authors' group's earlier mouse studies, combining dendritic-cell immunotherapy with celecoxib improved the immunotherapy compared with no treatment or either treatment alone.
  • In the authors' group's earlier mouse studies, zoledronic acid did not significantly change tumour progression or survival in living mice compared with untreated mice.
  • The authors argued that immunotherapy may lengthen survival without shrinking tumours on CT scans or improving progression-free survival, so standard response measures may not capture its benefit.
• The authors' conclusion: The authors concluded that because several cell types help the tumour survive, combination therapy targeting multiple cell types will probably be necessary.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Malignant Mesothelioma, Chemotherapy, Median Survival, Chronic Inflammation.

Related studies

• Dendritic cell-based immunotherapy in mesothelioma — R. Cornelissen, L.A. Lievense, et al. (2012)
• Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients — L.A. Lievense, K. Bezemer, et al. (2017)
• T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma — H. Vroman, G. Balzaretti, et al. (2020)
• Is immunotherapy a viable option in treating mesothelioma? — D.W. Dumoulin, J.G. Aerts, et al. (2017)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? — M. Lucchi, A. Picchi, et al. (2010)

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