PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer

Area of Science:

• Oncology
• Immunotherapy
• Biomarker Discovery

Background:

• The role of programmed death ligand-1 (PD-L1) messenger RNA (mRNA) from tumor-educated platelets (TEPs) in advanced non-small cell lung cancer (NSCLC) remains underexplored.
• Predicting clinical responses to immunotherapy in advanced NSCLC patients using TEP mRNA is an area of active investigation.
• Identifying novel biomarkers is crucial for enhancing clinical benefits and outcomes in NSCLC patients undergoing immunotherapy.

Purpose of the Study:

• To investigate the role and predictive value of TEP-derived PD-L1 mRNA in advanced NSCLC patients receiving immunotherapy.
• To assess the association between TEP-derived PD-L1 mRNA expression and tumoral PD-L1 expression.
• To determine if TEP-derived PD-L1 mRNA can serve as a surrogate biomarker for predicting immunotherapy response and progression-free survival (PFS).

Main Methods:

• Advanced NSCLC patients with wild-type EGFR/ALK treated with immunotherapy (alone or with chemotherapy) were enrolled.
• Tumoral PD-L1 expression was assessed via immunohistochemistry (IHC) for tumor proportion scores (TPS).
• PD-L1 mRNA levels in TEPs were quantified using RNA isolation and subsequent analysis.

Main Results:

• No significant correlation was found between TEP-derived PD-L1 mRNA and tumoral PD-L1 expression (r=-0.19, P=0.233).
• Patients with high TEP-derived PD-L1 mRNA showed significantly higher response rates (44.4%) compared to those with low levels (13.9%, P<0.01).
• High TEP-derived PD-L1 mRNA was associated with longer median progression-free survival (PFS) (8.3 months vs. 2.8 months, P<0.001), including in patients receiving immunotherapy alone.

Conclusions:

• This study provides the first data on TEP-derived PD-L1 mRNA in advanced NSCLC patients undergoing immunotherapy.
• TEP-derived PD-L1 mRNA demonstrates potential as a predictive biomarker for immunotherapy response and PFS in advanced NSCLC.
• Further research is warranted to validate TEP-derived PD-L1 mRNA as a surrogate biomarker for predicting overall survival.