Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.665133
Keywords
blood PD-L1; immune checkpoint inhibitors; NSCLC; exosome; biomarker
Categories
Funding
- National Natural Science Foundation of China [81602688, 81773245, 81972858]
- Natural Science Foundation of Chongqing [cstc2016jcyjA0531]
- Science and Technology Innovation Special Project of Chongqing Social Undertakings and Livelihood Security [cstc2017shmsA130108]
- Chongqing Innovation Leading Talents Program [cstccxljrc201910]
- Cultivation Program for Clinical Research Talents of Army Medical University [2018XLC1010]
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This study found that increased expression of PD-L1 mRNA and exoPD-L1 in the early stage of ICIs treatment may serve as positive biomarkers of efficacy and overall survival in advanced NSCLC patients.
Background Immune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic. Methods Paired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software. Results In 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA >= 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 >= 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment. Conclusion There was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.
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