Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study

Valmary‐Degano, Séverine; Colpart, Prudence; Villeneuve, Laurent; Monnien, Franck; Mhamdi, Loubna; Avérous, Gerlinde; Capovilla, Mathieu; Bibeau, Frédéric; Laverrière, Marie‐Hélène; Verriele-Beurrier, Véronique; Rejeb, Houda Ben; Dartigues, Peggy; Hommell-Fontaine, Juliette; Gilly, François-Noël; Isaac, Sylvie; Mery-Lamarche, Eliane; Abba, J.; Abboud, Karine; Alyami, Mohammad; Arvieux, C.; Bakrin, Naoual; Balagué, Gisèle; Barrau, Vincent; Béréder, Jean-Marc; Berton-Rigaud, Isabelle; Bonnefoy, Isabelle; Bouzard, D.; Bricault, Ivan; Brigand, Cécile; Carrère, Sébastien; Chaisemartin, Cécile de; Chassang, Madleen; Chevallier, A; Courvoisier, Thomas; Dohan, A.; Dromain, Clarisse; Dubreuil, Julien; Dumont, Frédéric; Eveno, Clarisse; Faruch-Bilfeld, Marie; Ferron, Gwénaël; Fournier, Laure; Gagnière, Johan; Geffroy, D.; Ghouti, Laurent; Gladieff, Laurence; Gléhen, Olivier; Goèré, Diane; Guibal, Aymeric; Guilloit, Jean-Marc; Guyon, Frédéric; Heyd, Bruno; Hoeffel, Christine; Hordonneau, Constance; Jourdan-Enfer, Peggy; Kaci, Rachid; Kianmanesh, Réza; Labbé-Devilliers, C.; Lacroix, Joëlle; Lelong, Bernard; Leroux-Broussier, A.; Lherm, Yoann; Dico, R. Lo; Lorimier, G.; Malhaire, Caroline; Marchal, Frédéric; Mariani, Pascale; Mathiotte, E.; Méeus, Pierre; Msika, Simon; Nadeau, C.; Ortega‐Deballon, Pablo; Passot, Guillaume; Pellet, Olivier; Peyrat, Patrice; Pezet, Denis; Pirrò, N.; Pocard, Marc; Poizat, Flora; Porcheron, J.; Poulet, A.; Quénet, François; Rat, Patrick; Rousselot, P.; Senellart, Hélène; Serrano, María José; Servois, Vincent; Sgabura, Olivia; Skanjeti, Andrea; Svrcek, Magali; Tétreau, Raphaël; Thibaudeau, Emilie; Touchefeu, Yann; Tuech, Jean‐Jacques; Vaudoyer, D.; Velasco, Stéphane; Wernert, Romuald; Zinzindohoué, Franck

doi:10.1016/j.ejso.2017.05.009

Cited by 23 publications

(12 citation statements)

References 31 publications

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“…None of the tumour cells in our samples expressed PDL1, which is in line with recently published data showing that PDL1 are rarely expressed in mesothelioma cells [ 37 ]. PD1-positive immune cells were found exclusively in E-MpMs, and they were located intratumoural and within ELSs in the large majority of cases.…”

Section: Discussionsupporting

confidence: 92%

Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types

Tazzari

Brich

Tuccitto

et al. 2018

Journal of Immunology Research

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Malignant peritoneal mesothelioma (MpM), arising in the setting of local inflammation, is a rare aggressive tumour with a poor prognosis and limited therapeutic options. The three major MpM histological variants, epithelioid (E-MpMs), biphasic, and sarcomatoid MpMs (S-MpMs), are characterised by an increased aggressiveness and enhanced levels of EZH2 expression. To investigate the MpM immune contexture along the spectrum of MpM histotypes, an extended in situ analysis was performed on a series of 14 cases. Tumour-infiltrating immune cells and their functionality were assessed by immunohistochemistry, immunofluorescence, qRT-PCR, and flow cytometry analysis. MpMs are featured by a complex immune landscape modulated along the spectrum of MpM variants. Tumour-infiltrating T cells and evidence for pre-existing antitumour immunity are mainly confined to E-MpMs. However, Th1-related immunological features are progressively impaired in the more aggressive forms of E-MpMs and completely lost in S-MpM. Concomitantly, E-MpMs show also signs of active immune suppression, such as the occurrence of Tregs and Bregs and the expression of the immune checkpoint inhibitory molecules PD1 and PDL1. This study enriches the rising rationale for immunotherapy in MpM and points to the E-MpMs as the most immune-sensitive MpM histotypes, but it also suggests that synergistic interventions aimed at modifying the tumour microenvironment (TME) should be considered to make immunotherapy beneficial for these patients.

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Section: Discussionsupporting

confidence: 92%

Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types

Tazzari

Brich

Tuccitto

et al. 2018

Journal of Immunology Research

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“…Our results showed that PD-L1 expression does not appear to be significantly associated with survival despite a trend toward a poorer prognosis with PD-L1 expression in ≥50% on tumor cells. The absence of a significant association with survival is in agreement with two recent studies, in which a specific antibody (SP142) (38) and four different antibodies were employed (17). This finding was observed even when we compared survival with PD-L1 expression on TILs, and with the combined expression of tumor cells and TILs.…”

Section: Pd-l1 ≥1% Pd-l1 <1% ----------------------------------------supporting

confidence: 92%

Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma

et al. 2019

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The tumor immune microenvironment (TME) and immune checkpoints have been reported to serve a role in the pathogenesis of malignant mesothelioma (MM) and treatment outcome. Additionally, mismatch Repair (MMR) deficiency appears to enhance the response to checkpoints blockade in several tumors. The aim of the present study was to analyze programmed death-1 ligand 1 (PD-L1) expression in MM and to characterize the TME. This could help to understand the immune response, and evaluate its prognostic and predictive values. We also investigated MMR protein expression. We retrospectively analyzed 55 mesotheliomas to determine PD-L1, CD4 + , CD8 + , mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and PMS1 homolog 2, mismatch repair system component (PMS2) expression. We used an immunoscore (1+, 2+ and 3+) to evaluate tumor-infiltrating lymphocytes (TILs). TILs were observed in all but two samples (53/55); the majority had an immunoscore 1+ (30/53), while 2+/3+ was reported for 23/53 samples. A predominance of CD8 + was highlighted in 8 cases (15%). PD-L1 expression of ≥1% on tumor cells was displayed in 40 cases; in 9 of these, ≥50% expression was reported. Of note, alterations in MMR staining was not observed. In addition, survival analysis revealed that epithelioid subtype was associated with better prognosis. We observed a trend towards poorer prognosis for ≥50% PD-L1 expression on tumor cells, lower immunoscore (1+) and CD8 + TIL predominance. The present study highlighted the importance of exploring the TME and the standardization of PD-L1 assessment guidelines to apply in the field of immunotherapy.

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“…Then, 299 duplicate publications were excluded, and 153 studies were screened by title and abstract. Subsequently, 119 studies were discarded and 34 studies 9 , 18 – 23 , 27 – 53 were left for eligibility assessment by full-text examination. Eighteen studies were excluded for different reasons: one study did not detect PD-L1 expression in sera samples other than tumor tissues, 37 11 studies did not present sufficient data for meta-analysis, 9 , 38 , 39 , 42 – 48 , 52 two studies did not use unique cut-off value, 40 , 50 one study did not test PD-L1 expression, 41 one study was a letter to the editor, 49 and two studies recruited patients with pleural and peritoneal mesothelioma tumors other than MPM.…”

Section: Resultsmentioning

confidence: 99%

“…Eighteen studies were excluded for different reasons: one study did not detect PD-L1 expression in sera samples other than tumor tissues, 37 11 studies did not present sufficient data for meta-analysis, 9 , 38 , 39 , 42 – 48 , 52 two studies did not use unique cut-off value, 40 , 50 one study did not test PD-L1 expression, 41 one study was a letter to the editor, 49 and two studies recruited patients with pleural and peritoneal mesothelioma tumors other than MPM. 51 , 53 Finally, 16 studies were included in our meta-analysis. 18 – 23 , 27 – 36 The flow chart of the article screening process is shown in Figure 1 .…”

Section: Resultsmentioning

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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Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study

Cited by 23 publications

References 31 publications

Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types

Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types

Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma

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

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