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

• Published in: Frontiers in immunology 2023-05, Vol.14, p.1157100-1157100
• Main Authors: Raza, Afsheen, Mohsen, Reyad, Kanbour, Aladdin, Zar Gul, Abdul Rehman, Philip, Anite, Vijayakumar, Suma, Hydrose, Shereena, Prabhu, Kirti S, Al-Suwaidi, Aisha Khamis, Inchakalody, Varghese Philipose, Merhi, Maysaloun, Abo El-Ella, Dina M, Tauro, Melissa Annrose, Akbar, Shayista, Al-Bozom, Issam, Abualainin, Wafa, Al-Abdulla, Rajaa, Sirriya, Shaza Abu, Hassnad, Suparna, Uddin, Shahab, Mohamed Ibrahim, Mohamed Izham, Al Homsi, Ussama, Demime, Said
• Format: Article
• Language: English
• Subjects: anti-PD-1; anti-PD-L1; Antineoplastic Agents, Immunological - pharmacology; Carcinoma, Non-Small-Cell Lung - pathology; CEA; Humans; Immunologic Factors - therapeutic use; Immunology; Lung Neoplasms - pathology; non-small cell lung cancer; predictive soluble biomarkers; Progression-Free Survival; tissue PD-L1; Treatment Outcome
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1157100

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