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Phenotypic and Proteomic Analysis Identifies Hallmarks of Blood Circulating Extracellular Vesicles in NSCLC Responders to Immune Checkpoint Inhibitors
- Source :
- Cancers, Vol 13, Iss 585, p 585 (2021), Cancers, Volume 13, Issue 4
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Simple Summary Purpose of this study was to investigate the prognostic and predictive role of blood circulating extracellular vesicles (EVs) in patients with advanced non-small cell lung cancer treated with immunotherapy. A newly optimized flow cytometry protocol was applied for identification and subtyping of blood circulating EVs in a total cohort of 59 NSCLC patients, which included 31 patients treated with anti-PD-1/PD-L1 agents and 28 patients treated with traditional chemotherapy. Our results show that pre-treatment concentration of blood circulating endothelial-derived EVs was correlated with overall survival and clinical response in patients treated with immunotherapy. Additionally, proteomic analysis of purified blood circulating EVs indicated differences in EV protein cargo between responders and non-responders to immunotherapy. These findings may pave the way to the identification of novel immunotherapy biomarkers in patients with advanced NSCLC. Abstract Immune checkpoint inhibitors (ICIs) induce durable clinical responses only in a subset of advanced non-small cell lung cancer (NSCLC) patients. There is a need to identify mechanisms of ICI resistance and immunotherapy biomarkers to improve clinical benefit. In this study, we evaluated the prognostic and predictive value of circulating endothelial and leukocyte-derived extracellular vesicles (EV) in patients with advanced NSCLC treated with anti-PD-1/PD-L1 agents. In addition, the relationship between total blood circulating EV proteome and response to ICIs was investigated. An optimized flow cytometry method was employed for the identification and subtyping of blood circulating EVs in 59 patients with advanced NSCLC. Blood samples were collected from patients receiving anti-PD-1/PD-L1 inhibitors (n = 31) or chemotherapy (n = 28). An exploratory proteomic analysis of sorted blood EVs was conducted in a subset of patients. Our results show that a low blood concentration of circulating endothelial-derived EVs before treatment was strongly associated to longer overall survival (p = 0.0004) and higher disease control rate (p = 0.045) in patients treated with ICIs. Interestingly, shotgun proteomics revealed that EVs of responders to anti-PD-1 therapy had a specific protein cargo before treatment. In addition, EV protein cargo was specifically modulated during immunotherapy. We identified a previously unknown association between circulating endothelial-derived extracellular vesicle concentration and immunotherapy-related clinical outcomes. We also observed differences in circulating extracellular vesicle proteome according to anti-PD-1-based treatment response in NSCLC patients. Overall, these results may contribute to the identification of novel circulating biomarkers for rational immunotherapy approaches in patients affected by NSCLC.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
lcsh:RC254-282
Article
Flow cytometry
immune checkpoint inhibitors
03 medical and health sciences
0302 clinical medicine
Cancer immunotherapy
medicine
Shotgun proteomics
non-small cell lung cancer
Chemotherapy
cancer immunotherapy
medicine.diagnostic_test
business.industry
Immunotherapy
Extracellular vesicle
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Proteome
Cancer research
Biomarker (medicine)
biomarker
business
extracellular vesicles
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 13
- Issue :
- 585
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....d8e16ac3d91914a17a317ba2bb8948fc