Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma

Our plain-English summary of Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma, by N. Sobhani, G. Roviello, T. Pivetta, et al (Molecular Biology Reports, 2019).

The study

• Authors: N. Sobhani, G. Roviello, T. Pivetta, A. Ianza, D. Bonazza, F. Zanconati, F. Giudici, C. Bottin, S.P. Corona, A. Guglielmi, C. Rizzardi, M. Milione, M. Cortale, M. Confalonieri, D. Generali
• Journal: Molecular Biology Reports
• Published: 2019;46(3):2713-2720
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

In plain English

This retrospective study examined archived tumour samples, held in Trieste, Italy, from 62 patients diagnosed with malignant pleural mesothelioma between 2005 and 2016. All were epithelioid type and selected as asbestos-exposed. No fiber types, jobs or amounts are given. The authors stained samples for immune cells around and within the tumour (tumour infiltrating lymphocytes, TILs) and the protein PD-L1. Survival was compared in the 50 patients who had died; TILs were measurable in 51 samples. Patients with moderate or high TILs around the tumour had median survival of 19 months (95% CI 9 to 25), versus 14 months (95% CI 6 to 16) with absent or low TILs (p = 0.02). TILs in other areas showed no statistically significant survival difference. PD-L1 positive patients tended to have shorter survival, but not statistically significantly (hazard ratio 1.76, 95% CI 0.92 to 3.36 within the tumour; 1.60, 0.80 to 3.19 in the stroma). No correlation between TILs and PD-L1 was found in 51 patients with both measurements. The authors concluded both are potential outcome predictors, noting their small sample.

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 study of archived tumour samples, relating immune-cell (TILs) and PD-L1 staining to overall survival
• Who was studied: 62 patients with epithelioid malignant pleural mesothelioma, diagnosed April 2005 to December 2016, with samples from the archive of the Institute of Pathological Anatomy of Trieste, Italy. 51 (82%) were male. TILs were measured on 51 samples and PD-L1 on all 62. Survival data were available for 50 patients; the 12 still alive were excluded from the survival analysis.
• Exposure: Patients were selected as having been exposed to asbestos. No fiber types, products, jobs or doses are reported. The factors actually studied were tumour infiltrating lymphocytes (CD3 staining) and PD-L1 expression.
• Main results:
  • Median overall survival for all patients was 18 months (95% CI 14 to 24). Survival time was available for 50 patients; the other 12 were still alive.
  • For TILs in the peritumoural region, patients in groups 2 plus 3 (moderate or high) had better survival than patients in groups 0 plus 1 (absent or low), p = 0.02.
  • Median survival was 19 months (95% CI 9 to 25) for patients with moderate or high peritumoural TILs, versus 14 months (95% CI 6 to 16) for those with absent or low peritumoural TILs.
  • For TILs in the intraepithelial, stromal and perivasal regions, no statistically significant difference in survival was seen.
  • Of 62 patients, tumour PD-L1 was positive in 25 (40.3%) and stromal PD-L1 was positive in 19 (30.2%).
  • PD-L1 positive patients had lower survival than PD-L1 negative patients, but the difference was not statistically significant. Intratumour PD-L1: hazard ratio 1.76 (p = 0.083, 95% CI 0.92 to 3.36). Stromal PD-L1: hazard ratio 1.60 (p = 0.176, 95% CI 0.80 to 3.19).
  • For intratumour PD-L1, median survival was 18 months (95% CI 9 to 24) without PD-L1 expression versus 12 months (95% CI 7 to 16) with PD-L1 expression.
  • For stromal PD-L1, median survival was 16 months (95% CI 10 to 22) without PD-L1 expression versus 14 months (95% CI 7 to 18) with PD-L1 expression.
  • In the 51 patients with both measurements, the authors did not find a correlation between TILs and PD-L1 expression (p = 1 for tumour PD-L1; p = 0.53 for stromal PD-L1).
• The authors' conclusion: The authors concluded that their research supports TILs and PD-L1 expression as potential outcome predictors in malignant pleural mesothelioma. They stated that using these markers to predict how well checkpoint inhibitors work needs future investigation. They also noted that PD-L1 was not statistically correlated with survival in their cohort.
• Limitations the authors state:
  • The sample was too small to compare the four TILs groups individually.
  • The lack of statistical significance for PD-L1 was probably due to the small sample and the low number of PD-L1 positive cases.
  • Only the epithelioid subtype was studied; other subtypes were not considered.
  • The reliability of PD-L1 measurement is affected by many variables, including antibodies and clones, staining protocols and platforms, and tumour heterogeneity.

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, Mesothelioma, Overall Survival, P-Value, Statistical Significance, Biomarker, checkpoint inhibitors.

Related studies

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• CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection — N. Yamada, S. Oizumi, et al. (2010)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)
• Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors — S. Hendry, R. Salgado, et al. (2017)
• PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma — B.H. Nguyen, R. Montgomery, et al. (2018)
• Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas — C. Combaz-Lair, F. Galateau-Sallé, et al. (2016)

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