Expression of PD-1/PD-L1 and PD-L2 in peripheral T-cells from non-small cell lung cancer patients

Area of Science:

• Immunology
• Oncology
• Biomarker Discovery

Background:

• The interaction between programmed death-1 (PD-1) and its ligands (PD-L1/2) inhibits T-cell activity, promoting tumor immune evasion.
• While anti-PD-1/PD-L1 therapies have advanced lung cancer treatment, the prognostic value of tumor PD-L1 expression is debated.
• Peripheral blood cell expression of PD-1, PD-L1, and PD-L2 could offer insights into prognosis and treatment response.

Purpose of the Study:

• To investigate the expression of PD-1, PD-L1, and PD-L2 in peripheral blood mononuclear cells (PBMCs) and lymphocyte subsets of non-small cell lung cancer (NSCLC) patients.
• To assess the correlation between PD-1, PD-L1, PD-L2 expression and overall survival (OS) in treatment-naïve advanced NSCLC patients.
• To explore the relationship between plasma cytokine levels and PD-1/PD-L1/PD-L2 expression on T-lymphocytes.

Main Methods:

• Prospective observational study involving 70 treatment-naïve advanced NSCLC patients (Stage IIIB/IV) and 10 healthy donors.
• Evaluation of plasma cytokine levels and PD-1, PD-L1, PD-L2 expression on circulating CD3+, CD3+CD4+, and CD3+CD8+ cells.
• Statistical analysis to correlate biomarker expression with overall survival.

Main Results:

• Higher percentages of PD-L1+CD3+, PD-L1+CD3+CD8+, PD-L2+PBMCs, PD-L2+CD3+, PD-L2+CD3+CD4+ cells were observed in NSCLC patients compared to healthy donors.
• Increased expression of PD-1, PD-L1, and PD-L2 on PBMCs and T-cell subsets was associated with decreased overall survival.
• Interleukin-2 (IL-2) and Tumor Necrosis Factor-alpha (TNF-α) showed the strongest association with PD-L1 and PD-L2 expression on specific T-lymphocyte subsets.

Conclusions:

• Elevated expression of PD-1, PD-L1, and PD-L2 in peripheral blood cells, particularly T-cells, may represent a mechanism of tumor immune escape in NSCLC.
• These peripheral biomarkers may hold prognostic value for advanced NSCLC patients.
• Further research is warranted to explore the clinical utility of these peripheral immune markers in NSCLC management.