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Background Immune checkpoint inhibitors (ICIs) have become a high-profile treatment regimen for malignancy in recent years. However, only a small piece of patients obtain benefit. How to use reasonable biomarkers to optimally select suitable patients is currently a research hot topic.
Methods Paired tissue samples and blood samples from 51 patients with various malignancies were collected for correlation analysis. Dynamic changes in bPD-L1 expression, including PD-L1 mRNA, soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) protein, were detected in non-small-cell lung cancer (NSCLC) patients treated with ICIs. The best cutoff values for progression-free survival (PFS) and OS of all three biomarkers were calculated with R software.
Results In 51 malignancies patients, those with positive tPD-L1 expression had significantly higher PD-L1 mRNA expression than those with negative tPD-L1 expression. For sPD-L1 expression, only the TC1~2/IC1~2 group had higher expression than the TC0/IC0 group. In 40 NSCLC patients, those with a fold change (2 months compared to baseline) of PD-L1 mRNA over 2.03 had a better PFS, a better OS and the best objective response (bOR) rate. In addition, a fold change of exoPD-L1 over 1.85 was also found to be associated with better efficacy and OS in a small cohort. Furthermore, the combination of the biomarkers could better screen patients who could benefit from ICI treatment.
Conclusion Blood PD-L1 expression was positively correlated with tPD-L1 expression. Increased expression of exoPD-L1, PD-L1 mRNA, or both during early treatment could serve as biomarkers for predicting efficacy and OS in NSCLC patients treated with ICIs.
Keywords
Blood PD-L1, immune checkpoint inhibitor, NSCLC, exosome, biomarker
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 15 Oct, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background Immune checkpoint inhibitors (ICIs) have become a high-profile treatment regimen for malignancy in recent years. However, only a small piece of patients obtain benefit. How to use reasonable biomarkers to optimally select suitable patients is currently a research hot topic.
Methods Paired tissue samples and blood samples from 51 patients with various malignancies were collected for correlation analysis. Dynamic changes in bPD-L1 expression, including PD-L1 mRNA, soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) protein, were detected in non-small-cell lung cancer (NSCLC) patients treated with ICIs. The best cutoff values for progression-free survival (PFS) and OS of all three biomarkers were calculated with R software.
Results In 51 malignancies patients, those with positive tPD-L1 expression had significantly higher PD-L1 mRNA expression than those with negative tPD-L1 expression. For sPD-L1 expression, only the TC1~2/IC1~2 group had higher expression than the TC0/IC0 group. In 40 NSCLC patients, those with a fold change (2 months compared to baseline) of PD-L1 mRNA over 2.03 had a better PFS, a better OS and the best objective response (bOR) rate. In addition, a fold change of exoPD-L1 over 1.85 was also found to be associated with better efficacy and OS in a small cohort. Furthermore, the combination of the biomarkers could better screen patients who could benefit from ICI treatment.
Conclusion Blood PD-L1 expression was positively correlated with tPD-L1 expression. Increased expression of exoPD-L1, PD-L1 mRNA, or both during early treatment could serve as biomarkers for predicting efficacy and OS in NSCLC patients treated with ICIs.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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