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

Mol Biol Rep. 2019 Jun;46(3):2713-2720. doi: 10.1007/s11033-019-04715-9. Epub 2019 Mar 6.

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.

Keywords: Immunotherapy; Malignant pleural mesothelioma; Programmed cell death-ligand 1; Tumour-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • B7-H1 Antigen / physiology
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / physiology
  • Male
  • Mesothelioma / genetics*
  • Mesothelioma / metabolism
  • Mesothelioma / mortality
  • Mesothelioma, Malignant
  • Middle Aged
  • Pleural Neoplasms / genetics
  • Prognosis
  • Retrospective Studies
  • Transcriptome / genetics
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human