Dynamics of Telomerase-Based PD-L1 Circulating Tumor Cells as a Longitudinal Biomarker for Treatment Response Prediction in Patients with Non-Small Cell Lung Cancer

TL;DR

This study introduces a new liquid biopsy method using telomerase activity to monitor cancer cells in lung cancer patients, helping predict treatment outcomes.

Contribution

The study introduces TelomeScan®, a novel method for detecting and monitoring PD-L1(+) circulating tumor cells in NSCLC patients.

Findings

TelomeScan® showed 75% sensitivity and 100% specificity for detecting PD-L1(+) cells.

PD-L1(+) and EMT(+) CTCs were found in 75% and 12% of patients, respectively.

Changes in PD-L1(+) CTC counts correlated with treatment response and disease progression.

Abstract

Noninvasive liquid biopsy for monitoring circulating tumor cells offers valuable insights for predicting therapeutic responses. We developed TelomeScan® (OBP-401), based on the detection of telomerase activity as a universal cancer cell marker and an indicator of the presence of viable circulating tumor cells (CTCs) for patients with advanced non-small cell lung cancer (NSCLC). This system evaluated CTC subtypes characterized by programmed death ligand 1 (PD-L1), an immune checkpoint molecule, and vimentin, an epithelial–mesenchymal transition (EMT) marker, using a multi-fluorescent color microscope reader. The prognostic value and therapeutic responses were predicted by dynamically monitoring CTC counts in 79 patients with advanced NSCLC. The sensitivity and specificity values of TelomeScan® for PD-L1(+) cells (≥1 cell) were 75% and 100%, respectively, indicating high diagnostic accuracy. PD-L1(+) and EMT(+) in CTCs were detected in 75% and 12% of patients, respectively. Detection of PD-L1(+)CTCs and PD-L1(+)EMT(+) CTCs before treatment was associated with poor prognosis (p < 0.05). Monitoring of reducing and increasing PD-L1(+) CTC counts in two sequential samples (baseline, cycle 2 treatment) correlated significantly with partial response (p = 0.032) and progressive disease (p = 0.023), respectively. Monitoring PD-L1(+)CTCs by TelomeScan® will aid in anticipating responses or resistance to frontline treatments, optimizing precision medicine choices in patients with NSCLC.

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