PD-L1 in tumor cells is the only used biomarker for anti PD1/PD-L1 immune-checkpoints inhibitors (ICI) in Non Small Cell Lung Cancer (NSCLC) patients. However, this parameter is inaccurate to predict response, especially in patients with low tumor PD-L1. Here, we evaluated circulating EVs as possible biomarkers for ICI in advanced NSCLC patients with low tumoral PD-L1. EVs were isolated from plasma of 64 PD-L1 low, ICI-treated NSCLC patients, classified either as responders (R; complete or partial response by RECIST 1.1) or non-responders (NR). EVs were characterized following MISEV guidelines and by flow cytometry. T cells from healthy donors were triggered in vitro using patients' EVs. Unsupervised statistical approach was applied to correlate EVs' and patients' features to clinical response. R-EVs showed higher levels of tetraspanins (CD9, CD81, CD63) than NR-EVs, significantly associated to better overall response rate (ORR). In multivariable analysis CD81-EVs correlated with ORR. Unsupervised analysis revealed a cluster of variables on EVs, including tetraspanins, significantly associated with ORR and improved survival. R-EVs expressed more costimulatory molecules than NR-EVs although both increased T cell proliferation and partially, activation. Tetraspanins levels on EVs could represent promising biomarkers for ICI response in NSCLC.
Circulating CD81-expressing extracellular vesicles as biomarkers of response for immune-checkpoint inhibitors in advanced NSCLC / Signorelli, Diego; Ghidotti, Patrizia; Proto, Claudia; Brambilla, Marta; De Toma, Alessandro; Ferrara, Roberto; Galli, Giulia; Ganzinelli, Monica; Lo Russo, Giuseppe; Prelaj, Arsela; Occhipinti, Mario; Viscardi, Giuseppe; Capizzuto, Valentina; Pontis, Francesca; Petraroia, Ilaria; Ferretti, Anna Maria; Colombo, Mario Paolo; Torri, Valter; Sozzi, Gabriella; Garassino, Marina Chiara; Jachetti, Elena; Fortunato, Orazio. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 13:(2022), p. 987639. [10.3389/fimmu.2022.987639]
Circulating CD81-expressing extracellular vesicles as biomarkers of response for immune-checkpoint inhibitors in advanced NSCLC
Occhipinti, Mario;
2022
Abstract
PD-L1 in tumor cells is the only used biomarker for anti PD1/PD-L1 immune-checkpoints inhibitors (ICI) in Non Small Cell Lung Cancer (NSCLC) patients. However, this parameter is inaccurate to predict response, especially in patients with low tumor PD-L1. Here, we evaluated circulating EVs as possible biomarkers for ICI in advanced NSCLC patients with low tumoral PD-L1. EVs were isolated from plasma of 64 PD-L1 low, ICI-treated NSCLC patients, classified either as responders (R; complete or partial response by RECIST 1.1) or non-responders (NR). EVs were characterized following MISEV guidelines and by flow cytometry. T cells from healthy donors were triggered in vitro using patients' EVs. Unsupervised statistical approach was applied to correlate EVs' and patients' features to clinical response. R-EVs showed higher levels of tetraspanins (CD9, CD81, CD63) than NR-EVs, significantly associated to better overall response rate (ORR). In multivariable analysis CD81-EVs correlated with ORR. Unsupervised analysis revealed a cluster of variables on EVs, including tetraspanins, significantly associated with ORR and improved survival. R-EVs expressed more costimulatory molecules than NR-EVs although both increased T cell proliferation and partially, activation. Tetraspanins levels on EVs could represent promising biomarkers for ICI response in NSCLC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
