Abstract 353P
Background
The PD-L1/PD-1 axis is a key immune escape mechanism in cancer. KRAS mutations can upregulate PD-L1 expression, intensifying immunosuppression. While studies primarily focus on the tumor microenvironment, emerging evidence highlights tumor-induced systemic immune disruptions. This study analyzed PD-L1 and PD-1 mRNA expression in PBMCs, explored their associations with KRAS mutations, and assessed their prognostic relevance in NSCLC patients.
Methods
A total of 128 NSCLC patients receiving first-line therapy at the University General Hospital of Heraklion were included. PBMCs were isolated using Ficoll density gradient centrifugation, and total RNA was extracted. Quantitative real-time PCR was performed for the target genes using PGK1 as the reference gene. Relative expression levels (2−ΔCT) were calculated and analyzed statistically.
Results
PD-L1 (p=0.023) and PD-1 (p=0.033) expression in PBMCs correlated positively with patient age. PD-L1 (p=0.014), but not PD-1 (p=0.402) expression was higher in female patients. No significant differences in PD-L1 (p=0.212) or PD-1 (p=0.473) expression in PBMCs were observed between patients with and without KRAS mutations in tumor tissue. Similarly, no associations were found between PD-L1 (p=0.625) or PD-1 (p=0.795) expression in PBMCs and PD-L1 expression in tumor tissue. Kaplan-Meier analysis showed that high PD-L1 expression in PBMCs (cutoff: 50th percentile, p=0.034) was associated with significantly longer overall survival (OS), whereas PD-1 expression showed no significant association with OS (p=0.062). Multivariate analysis confirmed high PD-L1 expression in PBMCs as an independent prognosticator of favorable OS in NSCLC (HR=0.604; p=0.029), irrespective of KRAS mutation status.
Conclusions
PD-L1 expression in PBMCs is a promising non-invasive biomarker for NSCLC patients. These findings underscore the potential of systemic immune profiling for prognostic assessment. Further studies are warranted to validate these results and investigate the expression of other immune checkpoint molecules and their impact on patients’ prognosis.
Funding
Hellenic Society of Medical Oncology (HeSMO).
Disclosure
All authors have declared no conflicts of interest.