Characterization of circulating tumor cells and its PD L1 expression with high sensitivity liquid biopsy panel in non small cell lung cancer patients

Early detection and intervention are crucial for long-term survival of either primary or recurrent lung cancer patients. Circulating tumor cells (CTCs) could be powerful biomarkers for the diagnosis, prognosis, and treatment planning of cancer. In this work we applied our FAST cytometer, a fiber-optic array scanning technology (FAST) to develop a sensitive diagnostic blood tests (“liquid biopsies”) for NSCLC. This technology is based on the ultra-rapid, sensitive and accurate detection of rare circulating cells expressing the biomarker(s) of interest. By applying the FAST cytometer with a unique NSCLC specific cocktail, we were able to detect CTC in NSCLC setting with higher sensitivity as compared with traditional cytokeratin-based detection. In a pilot cohort of 51 NSCLS patients, we have detected CTC in 74.2% using our unique panel for NSCLC CTC, this has raised our sensitivity from 48.8% using traditional cytokeratin-based detection. In addition, we have also interrogated circulating cancer associated fibroblasts (cCAF) as an additional liquid biopsy marker for NSCLC. We detected cCAF in 67% NSCLC patients. When combined with our enhanced CTC detection method, addition of cCAF further increased our sensitivity to 88.5%. Moreover, using clinically validated PD-L1 antibody (Ventana SP263) as reference, we have demonstrated our capacity to analyze PD-L1 expression on CTC at protein level, we have shown detection of PD-L1+ CTC in 80% of the patients. To summarize, we have developed an unique panel to detect CTC with higher sensitivity using combinational detection and we have demonstrated that by combining CTC detection with cCAF detection, liquid biopsy sensitivity for cancer detection can be further increased without significant increase in false positive rates. Lastly, we developed a method to analyze the PD-L1 expression on CTC using clinically validated Ventana PD-L1 (SP263) rabbit monoclonal antibody as reference which can potentially serve as a companion diagnostics tool for NSCLC immunotherapy Citation Format: Xiaohe Liu, Zheng Ao, Jordan S. Preiss, Joel Neal, Lisa Ya Zhou, Lidia Sambucetti, Heather A. Wakelee. Characterization of circulating tumor cells and its PD-L1 expression with high-sensitivity liquid biopsy panel in non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-238.