Blood-borne metastasis accounts for the bulk of morbidity and mortality of cancer patients. Rare circulating tumor cells (CTCs) hold the key to understanding the process of human cancer metastasis. We have developed robust on-chip image cytometry technology for high-throughput screening of rare disseminated tumor cells in blood or other body fluids. We are investigating the molecular signatures, functional activities, and metastatic potentials of these rare CTCs with the aim of understanding their diagnostic and prognostic values in the clinic.

An important arm in this direction is the blood-based neoantigen discovery for cancer immunotherapy. Neoantigen-specific T cells have been implicated as a major effector of checkpoint immunotherapies. However, the neoantigen repertoire and associated reactive T-cell populations have not been well explored – either at baseline or over the course of treatment. One challenge relates to the availability of tumor biopsies – a significant limiting factor for personalized immunotherapy. Moreover, the molecular profile of tumors evolves dynamically over time. But repeated biopsy sampling is seldom feasible for patients with cancers that require invasive biopsy procedures. CTCs are good surrogates that enable clinicians to repeatedly and non-invasively interrogate the mutational landscape and dynamic evolution of human cancer. They retain molecular signatures from both primary and metastatic lesions, thus allowing identifying truck/branch mutations and monitoring neoantigen landscape evolution during immunotherapy. Our on-chip image cytometry platform enables resolving neoantigen repertoire and antigen-reactive T-cell populations via CTCs and associated PBMCs isolated from patient blood samples. It holds the promise to deliver a simple and noninvasive tool for blood-based neoantigen discovery.