Efficiency of Immunological Blood Biomarkers in Predicting Chemotherapy Response and Survival Outcome for Non-Targetable Advanced Non-Small Cell Lung Cancer Patients

Purpose: Chemotherapy is the main therapy for non-targetable advanced non-small cell lung cancer (NSCLC). Nevertheless, few biomarkers are currently available for predicting clinical outcomes and monitoring treatment response. Patients and Methods: The blood samples of 42 patients with non-targetable advanced NSCLC who received chemotherapy were collected before chemotherapy and after chemotherapy. The circulating immune cells and subpopulation Treg were investigated using flow cytometry, and human immune checkpoint biomarker levels were analysed by multiplex bead-based assay. Results: After selecting the effective biomarkers for survival analysis, high pre-chemotherapy sCD25 (≥ 499.52 pg/mL; 4.52 vs 14.98 months, p = 0.030) and post-chemotherapy (≥ 515.23 pg/mL; 3.90 vs 21.25 months, p = 0.004) were associated with poorer median progression-free survival (PFS). An increase in pre-chemotherapy neutrophil to lymphocyte ratio (NLR) (ratio ≥ 6.9; 5.15 vs 21.54 months, p = 0.008) and post-chemotherapy NLR (ratio ≥ 3.1; 10-month OS 50.35% vs 83.57%, p = 0.014) was correlated with shorter overall survival (OS). Moreover, increased pre-chemotherapy %NKT cells (≥ 6.8%) were linked to improved clinical benefit rate (CBR) (2.72 vs 3.97 months, p = 0.013), while higher post-chemotherapy %NK cells (≥ 23.1%) were associated with rapid overall response rate (ORR) at 4 months (82.05% vs 25%, p = 0.035). Conclusion: Our findings suggest that sCD25 and NLR show potential as indicators of PFS and OS, respectively. Additionally, pre-chemotherapy %NKT and post-chemotherapy %NK cells may provide insight into monitoring chemotherapy response. This pilot study identified potential candidate biomarkers for further investigation to confirm their clinical utility. Keywords: non-targetable advanced NSCLC, immunological biomarkers, chemotherapy, survival outcomes, clinical response