Show simple item record

AuthorAkbar, Shayista
AuthorRaza, Afsheen
AuthorMohsin, Reyad
AuthorKanbour, Aladdin
AuthorQadri, Shahnaz
AuthorParray, Aijaz
AuthorZar Gul, Abdul Rehman
AuthorPhilip, Anite
AuthorVijayakumar, Suma
AuthorMerhi, Maysaloun
AuthorHydrose, Shereena
AuthorInchakalody, Varghese Philipose
AuthorAl-Abdulla, Rajaa
AuthorAbualainin, Wafa
AuthorSirriya, Shaza Abu
AuthorAl-Bozom, Issam
AuthorUddin, Shahab
AuthorKhan, Omar Muhammad
AuthorMohamed Ibrahim, Mohamed Izham
AuthorAl Homsi, Ussama
AuthorDermime, Said
Available date2023-05-28T06:26:52Z
Publication Date2023-01-18
Publication NameFrontiers in Immunology
Identifierhttp://dx.doi.org/10.3389/fimmu.2022.1097117
CitationAkbar, S., Raza, A., Mohsin, R., Kanbour, A., Qadri, S., Parray, A., ... & Dermime, S. (2022). Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients. Frontiers in Immunology, 13.
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85147210480&origin=inward
URIhttp://hdl.handle.net/10576/43477
AbstractImmune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p<0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p<0.0001; Nectin-2, p<0.0001; NT5E, p<0.0001; Siglec-7, p<0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p<0.0001; MICA, p<0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients.
SponsorThis research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-20-507 and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar.
Languageen
PublisherFrontiers Media S.A.
Subjectbiomarkers
cytokines
exosomes
follow-up
immune-checkpoint inhibitors
immune-oncological-checkpoints
NSCLC
TitleCirculating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients
TypeArticle
Volume Number13
ESSN1664-3224
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record