High levels of PD-L1 on platelets of NSCLC patients contributes to the pharmacological activity of Atezolizumab

• Published in: Biomedicine & pharmacotherapy Vol. 168; p. 115709
• Main Authors: Colarusso, Chiara, Falanga, Anna, Terlizzi, Michela, De Rosa, Ilaria, Somma, Pasquale, Sommella, Eduardo Maria, Caponigro, Vichy, Panico, Luigi, Salviati, Emanuela, Campiglia, Pietro, Salatiello, Giuseppe, Tramontano, Teresa, Maiolino, Piera, Pinto, Aldo, Sorrentino, Rosalinda
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2023
• Subjects: Immunotherapy; Non-small cell lung cancer (NSCLC); Platelets (PLTs); Survival rate; Tumor progression; Survival rate; Immunotherapy; Non-small cell lung cancer (NSCLC); Tumor progression; Platelets (PLTs)
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2023.115709

Several studies have associated platelets (PLTs) to NSCLC prognosis. To understand the role of PLTs in immunotherapy-treated patients, we used blood samples of NSCLC patients at different TNM stage. We found that PLTs count and the expression of PD-L1 (pPD-L1) were significantly higher in NSCLC patients at Stage IV than Stage I-III and healthy subjects. The presence of high pPD-L1 was associated to upregulated genes for the extracellular matrix organization and tumor immunosuppression. When patients’ survival was correlated to the levels of pPD-L1, longer survival rate was observed, but not when progression disease occurred. The in vitro stimulation of pPD-L1 with Atezolizumab induced CXCL4 release, accompanied by higher levels of TGFβ at the time of drug resistance when the levels of CD16, CD32 and CD64 significantly increased. Leiden-clustering method defined the phenotype of PLTs which showed that the ezrin-radixin-moesin (ERM) family proteins, underlying the PD-L1 signalosome, were involved in high pPD-L1 and higher survival rate. These data imply that Stage IV NSCLC patients characterized by high pPD-L1 are associated with longer progression-free survival rate because the blockade of pPD-L1 by Atezolizumab avoids the exacerbation of a T cell-mediated immune-suppressive environment. pPD-L1 could be an easy-to-use clinical approach to predict ICI responsiveness. [Display omitted] •NSCLC patients can be differentiated according to the level of PD-L1 on PLTs.•Stage IV patients with higher levels of pPD-L1 had longer progression-free survival probability than patients with low pPD-L1 because of the PD-L1 signalosome.•The in vitro interaction of pPD-L1 with atezolizumab inhibits PLTs to induce an immunosuppressive environment, but PLTs of patients treated with ICIs have lower levels of pPD-L1.•pPD-L1 can represent an easy-to-use clinical approach to predict ICI responsiveness.