TY - JOUR
T1 - Circulating levels of PD-L1 in mesothelioma patients from the NIBIT-MESO-1 study
T2 - Correlation with survival
AU - Chiarucci, Carla
AU - Cannito, Sara
AU - Daffinà, Maria Grazia
AU - Amato, Giovanni
AU - Giacobini, Gianluca
AU - Cutaia, Ornella
AU - Lofiego, Maria Fortunata
AU - Fazio, Carolina
AU - Giannarelli, Diana
AU - Danielli, Riccardo
AU - Di Giacomo, Anna Maria
AU - Coral, Sandra
AU - Calabrò, Luana
AU - Maio, Michele
AU - Covre, Alessia
N1 - Funding Information:
Funding: This research was funded in part by Fondazione Associazione Italiana per la Ricerca sul Cancro (AIRC) under 5 per Mille 2018, grant number ID.21073, P.I. Michele Maio, and by the Ministero della Salute, Bando Ricerca Finalizzata, grant number NET-2016-02361632, P.I. Michele Maio.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Biomarker
KW - Cancer immunotherapy
KW - Immune checkpoint inhibitors
KW - Mesothelioma
KW - PD-L1
KW - Soluble PD-L1
UR - http://www.scopus.com/inward/record.url?scp=85079455815&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079455815&partnerID=8YFLogxK
U2 - 10.3390/cancers12020361
DO - 10.3390/cancers12020361
M3 - Article
AN - SCOPUS:85079455815
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 361
ER -