Metastasis in cancer patients is reflected by measurable levels of circulating tumour cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumour burden of an individual patient.
Our study was designed to use microfluidic devices for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (HNC) and non-small cell lung cancer (NSCLC) patients were recruited to investigate the prognostic role of CTCs (n = 400).
We demonstrated a higher CTC capture efficiency using microfluidic CTC platforms. Molecular alterations present in the primary tissue were confirmed in the CTCs by DNA FISH (EGFR-amplification, ALK-translocations). The presence of CTC clusters was associated with the development of distant metastatic disease (P = 0.0313). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Likewise CTC cultures were established from 6/40 NSCLC samples. Exome sequencing of CTC and white blood cells (as germline control) confirmed the presence of somatic mutations in the CTC culture with mutational signatures consistent with NSCLC. Additionally our preliminary data indicate that PD-L1 is frequently expressed on CTCs in HNC and lung cancer and an immunoscore may be able to identify patients likely to benefit from immunotherapy.
Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular diversity present within the tumour, understanding of the disease progression and testing of therapies.
The author.
Has not received any funding.
The author has declared no conflicts of interest.