Extracellular vesicle PD‑L1 dynamics predict durable response to immune‑checkpoint inhibitors and survival in patients with non‑small cell lung cancer
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de Miguel-Perez, D... [et al.]. Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer. J Exp Clin Cancer Res 41, 186 (2022). [https://doi.org/10.1186/s13046-022-02379-1]
PatrocinadorCenter for Thoracic Oncology Icahn School of Medicine at Mount Sinai; Borsa Dottorati FSE XXXII ciclo Unime; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA016672; University of Pittsburgh Hillman Cancer Center; Hillman Cancer Center's NCI Cancer Center Support Grant (CCSG) P30CA047904; A.S.S.O. (Associazione Siciliana Sostegno Oncologico) Onlus; National Cancer Institute-Cancer Center Support Grant (CCSG) P30CA134274; Merck & Company
Background: Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods: Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results: As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion: These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.