Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma

Our plain-English summary of Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma, by S. Rovers, A. Janssens, J. Raskin, et al (Biomedicines, 2022).

The study

• Authors: S. Rovers, A. Janssens, J. Raskin, P. Pauwels, J.P. van Meerbeeck, E. Smits, E. Marcq
• Journal: Biomedicines
• Published: 2022;10(3)
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.

In plain English

This article is a review, not a new study. The authors summarized published laboratory, animal and clinical research on immune checkpoint inhibitor drugs for malignant pleural mesothelioma, a cancer the article describes as causally associated with asbestos exposure. They compared trials of single drugs with trials of drug combinations. Among the trials they cited, CheckMate 743 reported median overall survival of 18.1 months with ipilimumab plus nivolumab versus 14.1 months with cisplatin plus pemetrexed chemotherapy. Some single-drug trials, such as PROMISE-meso and DETERMINE, found no significant overall survival improvement. The authors noted that combinations caused more serious side effects. In the cited MAPS2 trial, grade 3 to 4 toxicities occurred in 26% of patients on the combination versus 14% on nivolumab alone. They then reviewed a newer drug target, TIGIT, mostly through studies in other cancers and in mice. They found only one study of TIGIT in mesothelioma. It reported TIGIT on 58.7% of tumor-infiltrating CD8+ T cells, compared with 33.4% of CD8+ cells from tumor-free lungs. The authors concluded that TIGIT blockade, possibly combined with anti-PD-(L)1 drugs, may hold promise, but that further studies are necessary.

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 preclinical and clinical evidence on immune checkpoint inhibitors in malignant pleural mesothelioma, including the potential of TIGIT blockade
• Who was studied: No new study population. The review covered published clinical trials of immune checkpoint inhibitors in malignant pleural mesothelioma (summarized in a table), plus laboratory and animal studies of TIGIT in other cancers and one study of TIGIT in mesothelioma
• Exposure: Not an exposure study. The review concerns immune checkpoint inhibitor drugs (for example nivolumab, ipilimumab, pembrolizumab, durvalumab, tremelimumab and anti-TIGIT antibodies). Asbestos is mentioned only as background, as the cause of malignant pleural mesothelioma
• Main results:
  • In the cited CheckMate 743 trial, median overall survival was 18.1 months with combined ipilimumab and nivolumab versus 14.1 months with cisplatin plus pemetrexed chemotherapy
  • In the cited PROMISE-meso trial in previously treated patients, response rate was 22% with pembrolizumab versus 6% with chemotherapy, but there was no significant improvement in overall survival
  • In the cited DETERMINE trial, median overall survival did not differ significantly between patients given tremelimumab (7.7 months) and those given placebo (7.3 months)
  • In the cited IFCT MAPS2 trial, grade 3 to 4 toxicities occurred in 26% of patients given ipilimumab plus nivolumab compared with 14% given nivolumab alone
  • In the only mesothelioma TIGIT study the authors found (Klampatsa et al.), TIGIT was expressed on 58.7% of CD8+ tumor-infiltrating lymphocytes from malignant pleural mesothelioma, compared with 33.4% of CD8+ cells from tumor-free lungs
  • In the cited CITYSCAPE trial in PD-L1-positive non-small cell lung cancer (not mesothelioma), response rate was 31.3% with tiragolumab plus atezolizumab versus 16.2% with atezolizumab alone
• The authors' conclusion: The authors concluded that TIGIT blockade and its combination with anti-PD-(L)1 drugs may hold promise as a new treatment for malignant pleural mesothelioma, but that further preclinical and clinical studies are necessary to investigate its potential
• Limitations the authors state:
  • The authors stated that data on TIGIT in mesothelioma are very limited; they identified what appears to be only one relevant study
  • The authors stated that a comprehensive analysis of trials combining checkpoint inhibitors with other agents was beyond the scope of the review
  • The authors stated that diagnostic and prognostic biomarkers of malignant pleural mesothelioma were beyond the scope of the review

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, checkpoint inhibitors, Immunotherapy, Mesothelioma, PD-L1.

Related studies

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• Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC — F. Facchinetti, A. Marabelle, et al. (2016)
• Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations — N. Principe, W.J. Aston, et al. (2022)
• Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma — L. Rondon, R. Fu, et al. (2023)
• Immune checkpoint blockade in malignant mesothelioma — L. Calabrò, M. Maio (2015)
• Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge — L. Calabrò, A. Morra, et al. (2018)

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