Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

Hotta, Katsuyuki; Fujimoto, Nobukazu

doi:10.1136/jitc-2019-000461

Cited by 26 publications

(27 citation statements)

References 61 publications

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“… 5 Moreover, immunotherapy with checkpoint blockade has emerged as a promising new treatment for unresectable MPM. 6 – 8 KEYNOTE-028 was the first clinical trial to show the benefit of immune checkpoint inhibition (ICI) in patients with MPM. 9 Although revolutionary advancements have been achieved in the treatment of MPM in the last decade, the prognosis for MPM has not substantially improved.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Jin¹,

Xie³

et al. 2020

Ther Adv Med Oncol

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Background: The prognostic value of programmed death-ligand 1 (PD-L1) expression in patients with malignant pleural mesothelioma (MPM) has been controversial according to previous investigations. Therefore, we conducted a meta-analysis to assess the potential prognostic significance of PD-L1 expression in MPM. Methods: PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were thoroughly searched for relevant original articles published before 9 April 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were calculated. The results of the meta-analysis were verified using The Cancer Genome Atlas (TCGA) dataset. Results: In total 16 studies were included in our meta-analysis. A high PD-L1 expression was associated with a poor OS (HR = 1.53, 95% CI = 1.28–1.83, p < 0.001), but not a grave PFS (HR = 1.07, 95% CI = 0.82–1.39, p = 0.643) in MPM. Furthermore, the PD-L1 expression correlated with the sarcomatoid + biphasic type of MPM (odds ratio = 4.32, 95% CI = 2.16–8.64, p < 0.001). TCGA data indicated that PD-L1 was a significant prognostic factor for OS (HR = 2.069, 95% CI = 1.136–3.769, p = 0.0175), but not for PFS (HR = 1.205, 95% CI = 0.572–2.539, p = 0.624), which was in accordance with the results of the meta-analysis. Conclusion: A high PD-L1 expression is a significant prognostic factor for poor OS of patients with MPM. We therefore suggest that PD-L1 expression levels can be used to predict the clinical outcomes of patients with MPM in the future.

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Section: Introductionmentioning

confidence: 99%

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Jin¹,

Xie³

et al. 2020

Ther Adv Med Oncol

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“…Considering the disappointing survival rate of MM patients following chemotherapy, other strategies have been investigated in recent years. Immunotherapy based on checkpoint inhibitors (ICI) has provided a significant improvement in overall survival for previously untreated unresectable MM [23]. In the recent CheckMate 743 trial, the combination of anti-programmed cell death 1 (PD-1, CD279) and anti-cytotoxic T-lymphocyte 4 (CTLA-4, CD152) antibodies (Nivolumab and Ipilimumab, respectively) increased the 2-year overall survival rate by 50% compared to platinum plus pemetrexed chemotherapy [24].…”

Section: Immune Checkpoint Blockade Therapy Requires Altered-self Antigensmentioning

confidence: 99%

Activation of DNA Damage Tolerance Pathways May Improve Immunotherapy of Mesothelioma

Brossel

Fontaine

Hoyos

et al. 2021

Cancers

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Immunotherapy based on two checkpoint inhibitors (ICI), programmed cell death 1 (PD-1, Nivolumab) and cytotoxic T-lymphocyte 4 (CTLA-4, Ipilimumab), has provided a significant improvement in overall survival for malignant mesothelioma (MM). Despite this major breakthrough, the median overall survival of patients treated with the two ICIs only reached 18.1 months vs. 14 months in standard chemotherapy. With an objective response rate of 40%, only a subset of patients benefits from immunotherapy. A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In MM, tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis (BAP1, NF2, CDKN2AB). In this opinion, we propose to investigate an approach based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response.

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“…However, despite the positive preliminary results, neither anti-CTLA-4 nor anti-PD-L1 provides successful benefits in a single treatment strategy; thus, further validation of clinical outcomes is still required in combinatory studies of a larger randomized trial. The most hopeful seems to be the anti-PD-1 immunotherapy in unresectable MPM cases [ 21 ].…”

Section: Novel Targeted Therapies Against Malignant Pleural Mesothelioma Cellsmentioning

confidence: 99%

Phytochemicals in Malignant Pleural Mesothelioma Treatment—Review on the Current Trends of Therapies

Chmielewska-Kassassir

Woźniak

2021

IJMS

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Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.

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Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

Cited by 26 publications

References 61 publications

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

Activation of DNA Damage Tolerance Pathways May Improve Immunotherapy of Mesothelioma

Phytochemicals in Malignant Pleural Mesothelioma Treatment—Review on the Current Trends of Therapies

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