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Serum 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

journal contribution
submitted on 2024-02-25, 09:04 and posted on 2024-02-25, 11:34 authored by Afsheen Raza, Reyad Mohsen, Aladdin Kanbour, Abdul Rehman Zar Gul, Anite Philip, Suma Vijayakumar, Shereena Hydrose, Kirti S. Prabhu, Aisha Khamis Al-Suwaidi, Varghese Philipose Inchakalody, Maysaloun Merhi, Dina M. Abo El-Ella, Melissa Annrose Tauro, Shayista Akbar, Issam Al-Bozom, Wafa Abualainin, Rajaa Al-Abdulla, Shaza Abu Sirriya, Suparna Hassnad, Shahab Uddin, Mohamed Izham Mohamed Ibrahim, Ussama Al Homsi, Said Demime

Non-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.

Other Information

Published in: Frontiers in Immunology
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Additional institutions affiliated with: Academic Health System - HMC and Qatar University Health - QU


Open Access funding provided by the Qatar National Library.



  • English



Publication Year

  • 2023

License statement

© 2023 The Authors. This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • National Center for Cancer Care and Research - HMC
  • Interim Translational Research Institute - HMC
  • Dermatology Institute - HMC
  • Sidra Medicine
  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar University
  • Laboratory Animal Research Center - QU
  • College of Pharmacy - QU HEALTH

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