Circulating levels of PD-L1 in mesothelioma patients from the NIBIT-MESO-1 study: Correlation with survival

Carla Chiarucci, Sara Cannito, Maria Grazia Daffinà, Giovanni Amato, Gianluca Giacobini, Ornella Cutaia, Maria Fortunata Lofiego, Carolina Fazio, Diana Giannarelli, Riccardo Danielli, Anna Maria Di Giacomo, Sandra Coral, Luana Calabrò, Michele Maio, Alessia Covre

Research output: Contribution to journalArticlepeer-review

Abstract

Targeting of the programmed cell death protein (PD)-1/programmed death-ligand 1 (PD-L1) axis has shown a significant clinical impact in several tumor types. Accordingly, our phase II NIBIT-MESO-1 study demonstrated an improved clinical efficacy in mesothelioma patients treated with the anti-PD-L1 durvalumab combined with the anti-cytotoxic T-lymphocyte antigen (CTLA)-4 tremelimumab, as compared to tremelimumab alone. Due to the promising therapeutic activity of immune check-point inhibitors (ICIs) in mesothelioma patients, the identification of biomarkers predictive of response to treatment is of crucial relevance. The prognostic role of soluble PD-L1 (sPD-L1) proposed in cancer patients prompted us to investigate this protein in sera from mesothelioma patients (n = 40) enrolled in the NIBIT-MESO-1 study. A significant (p < 0.001) increase in sPD-L1 levels was detected in patients after the first cycle and during therapy vs. baseline. A longer overall survival (OS) was observed in patients with sPD-L1 concentrations below (at baseline, d1C2, d1C5 (p < 0.01)) or FC values above (p < 0.05 at d1C2, d1C3, d1C5) their statistically calculated optimal cut-offs. On the basis of these initial results, the specific role of CTLA-4-, PD-L1-, or PD-1-targeting on sPD-L1 release was then investigated in sera from 81 additional ICI-treated solid cancer patients. Results showed a significant (p < 0.001) increase of sPD-L1 levels during therapy compared to baseline only in anti-PD-L1-treated patients, supporting the specific involvement of PD-L1 targeting in the release of its soluble form. Our findings suggest that sPD-L1 represents a predictive biomarker of clinical response to anti-PD-L1 cancer immunotherapy.

Original languageEnglish
Article number361
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Biomarker
  • Cancer immunotherapy
  • Immune checkpoint inhibitors
  • Mesothelioma
  • PD-L1
  • Soluble PD-L1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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