High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab.

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen (CEA), human Telomerase Reverse Transcriptase (hTERT), cytokeratin19 (CK19), and programmed death ligand-1 (PD-L1) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab. The CTC chip effectively enriched cells from lung cancer cell line PC-9. The large cell fraction had a high expression of CEA and hTERT, with the former being significantly associated with the clinical response to nivolumab. The expression of CEA and hTERT in CTCs derived from the blood of a patient with lung cancer were also validated. The evaluation of CEA and possibly hTERT in CTCs collected by the CTC chip may represent a promising predictive blood marker for sensitivity to nivolumab. To the best of our knowledge this is the first report to describe the predictive CTC marker for nivolumab in pre-treatment patients.