Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM)

Our plain-English summary of Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM), by S. Cedrés, S. Ponce-Aix, J. Zugazagoitia, et al (PloS One, 2015).

The study

• Authors: S. Cedrés, S. Ponce-Aix, J. Zugazagoitia, I. Sansano, A. Enguita, A. Navarro-Mendivil, A. Martinez-Marti, P. Martinez, E. Felip
• Journal: PloS One
• Published: 2015;10(3):e0121071
• Cited by: 161 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The increasing incidence and poor outcome associated with MPM requires finding effective treatment for this disease. PD1/PD-L1 pathway plays a central role in tumor immune evasion and appears to be predictive and prognostic marker. PD-L1 is expressed in many different human cancers but its role in MPM has yet to be established. The aim of this study is to evaluate the expression of PD-L1 in MPM.

Methods: 119 MPM patients (p) from two institutions between November 2002 and February 2014 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained with anti-PD-L1 (clone E1L3N). Cases showing more than 1% of tumor cells expression of PD-L1 were considered positive.

Results: PD-L1 was analyzed in 77 p with tumor tissue available and was positive in 20.7% p (14 samples in membrane, 16 in cytoplasm and 4 in immune infiltrate). PD-L1 intensity was weak in 56.2%, moderate in 25% and strong in 18.7% p. There was a significant relationship between PD-L1 expression and histology (PD-L1 expression 37.5% in no-epithelioid tumor and 13.2% in epithelioid; p=0.033). The median survival in p PD-L1 positive was 4.79 vs 16.3 months in p PD-L1 negative (p=0.012).

Conclusions: We have shown PD-L1 is expressed in 20% of patients, associated with no epithelioid histology and poor prognostic in MPM. Our results suggest PD-L1 warrants further exploration in selecting p for immunotherapy.

In plain English

This study examined whether tumors from people with malignant pleural mesothelioma (MPM) carry PD-L1, a protein that helps tumors evade the immune system. The authors reviewed 119 consecutive MPM patients from two hospitals in Barcelona and Madrid, Spain. PD-L1 testing on tumor tissue was available for 77 of them. In the whole group, 44.5% had previous asbestos exposure; the article does not report fiber types. Of the 77 tumors tested, 16 (20.8%) were PD-L1 positive. Positivity was more common in non-epithelioid tumors (9 of 24, 37.5%) than in epithelioid tumors (7 of 53, 13.2%). PD-L1 did not correlate with asbestos exposure, sex, stage or chemotherapy regimen. Median survival was 4.8 months for PD-L1 positive patients and 16.3 months for PD-L1 negative patients. PD-L1 remained a significant survival factor in a multivariate analysis (hazard ratio 2.08, 95% CI 1.12 to 3.88). The authors noted that some sub-analyses were exploratory with few patients, and that other factors could influence prognosis. They concluded that PD-L1 is a candidate marker that warrants further exploration for selecting MPM patients for immunotherapy.

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: Retrospective analysis of two hospital cohorts, using immunohistochemistry (tissue staining) for PD-L1 on stored tumor tissue, compared with clinical features and survival
• Who was studied: 119 consecutive patients with histologically proven malignant pleural mesothelioma at Vall d'Hebron University Hospital (Barcelona) and 12 de Octubre University Hospital (Madrid), Spain, collected January 2000 to April 2014 according to the methods section. The abstract gives November 2002 to February 2014. Median age was 69 years and 71.4% were male. Tumor tissue for PD-L1 analysis was available for 77 patients.
• Exposure: The main factor studied was PD-L1 expression in tumor tissue, measured with the E1L3N antibody. Asbestos exposure was recorded as a clinical characteristic: yes in 53 of 119 (44.5%), no in 38 (31.9%), no data in 28 (23.5%). No fiber types, products, jobs or doses are reported.
• Main results:
  • Of the 77 tumor samples examined, 16 (20.8%) expressed PD-L1 and 61 (79.2%) were negative
  • All 16 positive cases showed staining in the cytoplasm, 14 also in the cell membrane, and 4 also in infiltrating lymphocytes
  • Among the 16 positive patients, staining intensity was weak in 9 (56.2%), moderate in 4 (25%) and strong in 3 (18.8%)
  • PD-L1 positivity was more frequent in non-epithelioid tumors (9 of 24 patients, 37.5%) than in epithelioid tumors (7 of 53 patients, 13.2%), p = 0.033
  • PD-L1 expression did not correlate with gender, asbestos exposure, clinical stage, chemotherapy regimen, response to treatment or tumor-infiltrating lymphocytes. In Table 2, asbestos exposure was recorded in 5 (32%) of PD-L1 positive and 31 (51%) of PD-L1 negative patients, p = 0.14.
  • In the whole cohort of 119 patients, survival did not differ according to gender, smoking, asbestos exposure or tumor side
  • Median survival was 4.8 months for PD-L1 positive patients and 16.3 months for PD-L1 negative patients (p = 0.012)
  • In multivariate Cox regression, PD-L1 remained a significant prognostic factor for survival: HR 2.08, 95% CI 1.12 to 3.88, p = 0.021
• The authors' conclusion: The authors concluded that PD-L1 expression in MPM is associated with non-epithelioid histology and survival. They suggested it is a candidate molecular marker that warrants further exploration for selecting MPM patients for immunotherapy.
• Limitations the authors state:
  • The survival analyses by staining intensity and by percentage of stained tumor cells were exploratory, involved a small number of patients, and must be interpreted carefully
  • The authors could not exclude other factors that might influence prognosis
  • Thresholds for PD-L1 positivity have not been clearly defined for all PD-L1 antibodies, and definitions vary across studies

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, Histology, Epithelioid, Median Overall Survival, Immunotherapy.

Related studies

• Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2016)
• Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status — E. Rrapaj, L. Giacometti, et al. (2021)
• Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland — D. Vizcaya, B. Farahmand, et al. (2020)
• Prognostic Role of Programmed Cell Death 1 Ligand 1 in Resectable Pleural Mesothelioma — H.S. Lee, M. Hamaji, et al. (2021)
• Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis — F. Zhang, W. Gong (2020)
• Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas — K. Otsubo, H. Sakai, et al. (2021)

Browse more research in PloS One, or return to medical research.