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AuthorRaza, Afsheen
AuthorMohsen, Reyad
AuthorKanbour, Aladdin
AuthorZar Gul, Abdul Rehman
AuthorPhilip, Anite
AuthorVijayakumar, Suma
AuthorHydrose, Shereena
AuthorPrabhu, Kirti S.
AuthorAl-Suwaidi, Aisha Khamis
AuthorInchakalody, Varghese Philipose
AuthorMerhi, Maysaloun
AuthorAbo El-Ella, Dina M.
AuthorTauro, Melissa Annrose
AuthorAkbar, Shayista
AuthorAl-Bozom, Issam
AuthorAbualainin, Wafa
AuthorAl-Abdulla, Rajaa
AuthorSirriya, Shaza Abu
AuthorHassnad, Suparna
AuthorUddin, Shahab
AuthorMohamed Ibrahim, Mohamed Izham
AuthorAl Homsi, Ussama
AuthorDemime, Said
Available date2023-11-05T06:14:31Z
Publication Date2023
Publication NameFrontiers in Immunology
ResourceScopus
ISSN16643224
URIhttp://dx.doi.org/10.3389/fimmu.2023.1157100
URIhttp://hdl.handle.net/10576/49025
AbstractNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.
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. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Acknowledgments
Languageen
PublisherFrontiers Media S.A.
Subjectanti-PD-1
anti-PD-L1
CEA
non-small cell lung cancer
predictive soluble biomarkers
tissue PD-L1
TitleSerum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression
TypeArticle
Volume Number14
dc.accessType Open Access


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