Online citations, reference lists, and bibliographies.
← Back to Search

Molecular And Histopathological Characterization Of The Tumor Immune Microenvironment In Advanced Stage Of Malignant Pleural Mesothelioma

N. S. Patil, L. Righi, H. Koeppen, W. Zou, S. Izzo, F. Grosso, R. Libener, M. Loiacono, V. Monica, C. Buttigliero, S. Novello, P. Hegde, M. Papotti, M. Kowanetz, G. Scagliotti
Published 2018 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Introduction Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and relatively chemoresistant and radioresistant malignancy with limited therapeutic options. Our objective was to investigate the prevalence of programmed death ligand 1 (PD‐L1) and the characteristics of the immune environment in this disease. Methods A total of 99 archival tumors from advanced‐stage MPM were immunohistochemically tested in parallel for PD‐L1 in two different laboratories, and 87 of them were profiled for immune gene expression by NanoString analysis for 800 genes. A prior study on the same samples indicated a low mutational load with a complex mutational landscape of genetic variations more frequently associated with the p53/DNA repair and phosphoinisitide‐3‐kinase pathways. Results PD‐L1 expression was found in 16% of the MPM tumor samples, either in the tumor cells or the infiltrating immune cells. Gene expression analysis suggested that MPM is an inflamed tumor type and can be classified into three different subgroups on the basis of the different expression profiles of immune‐related genes, of which two groups showed varying degrees of expression of immune‐related genes. Overall, these molecular findings suggest that these subgroups of MPM associated with PD‐L1 positivity and expression of immune‐related genes accounting for 60% of MPMs represent a candidate subtype that may respond to cancer immunotherapy. Conclusions These data suggest that 60% of patients with MPM characterized by either PD‐L1 expression or an inflamed status are attractive candidates for cancer immunotherapeutic options.
This paper references
10.1158/1078-0432.CCR-16-0066
Genomic Approaches to Understanding Response and Resistance to Immunotherapy
D. Braun (2016)
Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis.
W. Zhou (2015)
10.1038/ng.3520
Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations
R. Bueno (2016)
10.1038/icb.2010.88
CD40‐activated B cells contribute to mesothelioma tumor regression
C. Jackaman (2011)
10.1371/journal.pone.0127600
Ribonucleotide Reductase Subunit M2 Predicts Survival in Subgroups of Patients with Non-Small Cell Lung Carcinoma: Effects of Gender and Smoking Status
V. Mah (2015)
10.1165/rcmb.2013-0472TR
Immunotherapy for malignant pleural mesothelioma. Current status and future prospects.
R. Wong (2014)
10.1002/0471142727.mb25b10s94
Digital multiplexed gene expression analysis using the NanoString nCounter system.
Meghana Kulkarni (2011)
10.7150/jca.16390
Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy
R. F. Walter (2016)
10.1016/j.jtho.2017.02.013
The Immune Microenvironment, Genome‐wide Copy Number Aberrations, and Survival in Mesothelioma
B. Thapa (2017)
10.1200/JCO.2015.63.7421
Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study.
D. McDermott (2016)
10.1016/j.jtho.2016.07.033
Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD‐L1 and the PD‐L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti–PD‐L1 Antibody Avelumab
Swati Khanna (2016)
10.1016/S0140-6736(16)00587-0
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
L. Fehrenbacher (2016)
10.1158/1078-0432.CCR-15-1507
The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition
P. Hegde (2016)
10.1200/JCO.2014.59.0703
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
R. Motzer (2015)
10.1097/JTO.0000000000000436
Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study
M. Lo Iacono (2015)
10.1016/S0140-6736(16)32517-X
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial
A. Rittmeyer (2017)
10.1158/0008-5472.CAN-14-1008
Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.
Guangwu Guo (2015)
10.1016/j.ctrv.2015.09.006
Targeting immune checkpoints: New opportunity for mesothelioma treatment?
E. Marcq (2015)
10.1158/2326-6066.CIR-16-0171
Cytotoxic T Cells in PD-L1–Positive Malignant Pleural Mesotheliomas Are Counterbalanced by Distinct Immunosuppressive Factors
M. Awad (2016)
10.1016/S0140-6736(16)00561-4
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial
J. Rosenberg (2016)
10.1165/rcmb.2010-0435OC
Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.
M. Maeda (2011)
10.1016/j.jtho.2016.05.020
The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing
Marieke Hylebos (2016)
10.1080/17425255.2017.1277204
Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma
R. Patel (2017)
10.18632/ONCOTARGET.4253
Reactive oxygen species a double-edged sword for mesothelioma
S. Benedetti (2015)
10.1038/ng.855
The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma
Matthew J Bott (2011)
10.1200/JCO.2003.11.136
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
10.1155/2015/302649
Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer
F. Grossi (2015)
10.1016/j.lungcan.2015.05.014
Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England.
R. Damhuis (2015)
10.1016/j.ctrv.2015.05.001
The established and future biomarkers of malignant pleural mesothelioma.
V. Panou (2015)
10.1200/JCO.2009.25.9275
Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy.
L. Righi (2010)
10.1016/j.critrevonc.2016.02.001
PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis.
S. Gandini (2016)
10.1158/1078-0432.CCR-13-2429
Molecular Classification of Malignant Pleural Mesothelioma: Identification of a Poor Prognosis Subgroup Linked to the Epithelial-to-Mesenchymal Transition
A. de Reyniès (2014)
10.1016/j.humpath.2016.01.010
Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas.
Christelle Combaz-Lair (2016)
10.1097/JTO.0000000000000177
B7-H1 Expression in Malignant Pleural Mesothelioma is Associated with Sarcomatoid Histology and Poor Prognosis
A. Mansfield (2014)
10.1038/sj.bdj.2016.860
Nivolumab for recurrent squamous-cell carcinoma of the head and neck
J. Radford (2016)
10.1155/2012/492608
Asbestos-Induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis
H. Matsuzaki (2012)
10.1371/journal.pone.0121071
Analysis of Expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Malignant Pleural Mesothelioma (MPM)
S. Cedrés (2015)
10.1038/cdd.2015.165
Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease
T. Chernova (2016)
10.18632/oncotarget.7666
microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma
R. F. Walter (2016)
10.1056/NEJMoa1503093
Pembrolizumab versus Ipilimumab in Advanced Melanoma.
C. Robert (2015)
Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC
WD Travis (2015)
[Systemic Treatment of Malignant Pleural Mesothelioma].
T. Nakano (2017)
10.1007/s13277-014-2592-7
Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy
H. Zhao (2014)



This paper is referenced by
10.1097/MCP.0000000000000489
Updates in the diagnosis and treatment of malignant pleural mesothelioma
D. Katzman (2018)
10.1186/s13039-020-00511-4
Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines
Eva Wahlbuhl (2020)
10.1177/1758835920962362
PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study
Liu Jin (2020)
10.3389/fonc.2019.01366
The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy
G. Chu (2019)
10.1016/j.thorsurg.2020.08.005
The Molecular Basis of Malignant Pleural Mesothelioma.
Benjamin Wadowski (2020)
10.1016/j.rmed.2018.06.026
A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma.
F. Petrelli (2018)
10.1007/s00432-020-03457-7
Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis
R. Carosio (2020)
10.1016/j.jtho.2018.02.021
Progress in the Management of Malignant Pleural Mesothelioma in 2017
Amanda J McCambridge (2018)
10.1111/pin.13028
Expression status of PD-L1 and B7-H3 in mesothelioma.
E. Matsumura (2020)
10.1016/j.jtho.2019.03.029
Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.
I. C. Salaroglio (2019)
10.1007/s12032-018-1156-x
Is there a role for immunotherapy in malignant pleural mesothelioma?
A. Tartarone (2018)
10.1016/j.fsi.2018.08.052
Comparative transcriptomics analysis of the river pufferfish (Takifugu obscurus) by tributyltin exposure: Clues for revealing its toxic injury mechanism
Dong-po Xu (2018)
10.1007/978-3-030-16884-1_5
Microenvironment and Immunology of the Human Pleural Malignant Mesothelioma
Elisabeth Digifico (2019)
10.1101/2020.08.14.20174789
Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification
A. Alay (2020)
Immunotherapy for mesothelioma: rationale and new approaches.
Joshua E Reuss (2020)
10.1016/j.intimp.2020.106481
Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis.
F. Zhang (2020)
10.1101/2020.06.16.154815
Asbestos accelerates disease onset in a genetic model of Malignant Pleural Mesothelioma
Pooyeh Farahmand (2020)
10.1016/j.jtho.2020.03.006
Immune checkpoint inhibitors in thoracic malignancies: Review of the existing evidence by an IASLC expert panel and recommendations.
J. Remon (2020)
10.1016/j.jtocrr.2020.100075
Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population
Tamkin Ahmadzada (2020)
10.1016/j.jtho.2018.02.021
State of the Art : Advances in Malignant Pleural Mesothelioma in 2017
Amanda J McCambridge (2018)
10.3390/jcm9072153
Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?
Y. Ichiki (2020)
10.3390/ijms19041041
Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma
J. Minnema-Luiting (2018)
10.1080/14712598.2019.1606209
Immune checkpoint inhibition for the treatment of mesothelioma
A. Nowak (2019)
10.1158/1078-0432.CCR-19-0103
Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT)
M. Okada (2019)
Semantic Scholar Logo Some data provided by SemanticScholar