Combination of plasma MMPs and PD-1-binding soluble PD-L1 predicts recurrence in gastric cancer and the efficacy of...

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• The tumor microenvironment (TME) significantly influences the effectiveness of immune checkpoint inhibitors (ICIs).
• Currently, no reliable liquid biomarkers exist to assess TME heterogeneity.
• This study explores the clinical significance of PD-1-binding soluble PD-L1 (bsPD-L1) in gastric cancer (GC) and non-small cell lung cancer (NSCLC) patients undergoing ICI therapy.

Purpose of the Study:

• To investigate the clinical utility of bsPD-L1 as a biomarker in GC and NSCLC.
• To correlate bsPD-L1 levels with other TME components like matrix metalloproteinases (MMPs) and IFN-γ.
• To assess the predictive value of bsPD-L1 and MMPs for ICI treatment outcomes.

Main Methods:

• Plasma samples from 117 GC patients and 72 NSCLC patients were analyzed for bsPD-L1, MMPs, and IFN-γ.
• Tumor tissues from 25 GC patients were examined for extracellular matrix (ECM) integrity, PD-L1 expression, and T cell infiltration.
• Patients received PD-1/PD-L1 blockade therapy.

Main Results:

• bsPD-L1 was detected in a subset of GC and NSCLC patients.
• bsPD-L1 correlated with MMP13 and MMP3 levels, IFN-γ, and T cell infiltration in GC.
• Combined bsPD-L1 and MMP status demonstrated higher predictive accuracy for prognosis than tumor PD-L1 expression alone.

Conclusions:

• Plasma bsPD-L1 and MMP13 levels can indicate T cell response and ECM integrity loss within the TME.
• The combination of bsPD-L1 and MMPs offers a potential non-invasive tool for predicting GC recurrence and NSCLC ICI efficacy.