Dynamic Monitoring of CTCs and EVs to Predict Chemoimmunotherapy Efficacy in Lung Cancer

Background: Circulating tumor cells (CTCs), programmed cell death-ligand 1 (PD-L1) positive CTCs (PD-L1+CTCs) and extracellular vesicles (EVs) are important biomarkers for predicting treatment efficacy. This study comprehensively investigated the factors used to forecast chemoimmunotherapy efficacy in advanced lung cancer. Methods: The CellSearch system, EVAnalyzer plugin and single-cell whole-exome sequencing (WES) were used to analyze these factors. Results: It was found that CTCs were highly detectable in advanced lung cancer. The median number of baseline CTCs was significantly lower in non-small cell lung cancer (NSCLC) than small cell lung cancer (SCLC) (3 vs. 38, p < 0.0001), as were PD-L1+CTCs (1 vs. 5, p = 0.0014). PD-L1+CTCs decreasing after two treatment circles was associated with superior ORR. Baseline median EV counts were elevated in NSCLC compared with SCLC (11,700 vs 1371, p = 0.017). Patients exhibiting divergent dynamic trends between EVs and CTC/PD-L1+CTCs demonstrated better treatment response. The combination of CTCs, PD-L1+CTCs and EVs improved predictive efficacy for both NSCLC and SCLC. CTC sequencing identified multiple pathogenic somatic variants, which might affect immunotherapy efficacy. Conclusions: Serial dynamic monitoring of CTCs, PD-L1+CTCs and EVs, as well as CTC sequencing, enables the early prediction of chemoimmunotherapy response and the discovery of mechanisms that affect immunotherapy efficacy in advanced lung cancer.