The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma

Aim: There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome.Methods: Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity.Results: Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484).Conclusions: Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time.

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“…17 In our cohort, 24 patients out of 42 patients with positive PD-L1 expression were found to also be TILs positive (57%).…”

Section: Discussionmentioning

confidence: 60%

PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

Nguyen

Montgomery

Fadia

et al. 2017

Asia-Pac J Clncl Oncology

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“…Approximately 40% of tumours express PDL1, which is associated with non-epithelioid histology and worse outcome for high expressing tumours 124 . Keynote 28 is the first phase Ib trial to report on the activity of pembrolizumab in patients with pleural mesothelioma and enrolled 25 patients harbouring PDL1-positive tumours 125 .…”

Section: Section 11: Systemic Anticancer Treatmentmentioning

confidence: 99%

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

Woolhouse

Bishop

Darlison

et al. 2018

Thorax

178

219

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“…New horizons from immunotherapy in malignant pleural mesothelioma immunotherapy (15,16). Along this line, a number of immunotherapeutic clinical trials, aimed at activating the host's immune system or overcoming components of the immunosuppressive tumor microenvironment, have been activated (17).…”

Section: Review Articlementioning

confidence: 99%

New horizons from immunotherapy in malignant pleural mesothelioma

Calabrò¹,

Maio²

2018

J. Thorac. Dis.

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Malignant pleural mesothelioma (MPM) is an aggressive disease with a severe prognosis. Medical treatment for MPM unresectable patients is still unsatisfactory; therefore novel therapeutic approaches are urgently needed. Immunotherapy represents a promising treatment for MPM patients. Here, we'll discuss the most promising immunotherapeutic treatments currently under active investigation for this still dreadful disease.

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The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma

Abstract: PD-L1 expression was associated with nonepithelioid MPM, poor clinical outcome, and increased immunological infiltrates. Increased genomic instability did not correlate with PD-L1 expression but was associated with poorer survival.

Cited by 87 publications

References 35 publications

PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

New horizons from immunotherapy in malignant pleural mesothelioma

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