Evaluating tumor cell- and T cell-derived extracellular vesicles as potential biomarkers of cancer and immune cell competence

ABSTRACT

Introduction

Extracellular vesicles (EVs) produced by tumors, also called tumor-derived exosomes (TEX), have been implicated in inducing immune cell suppression in vitro and in vivo. The development of a novel category of noninvasive biomarkers for precision oncology remains an unmet need, and TEX emerge as a promising liquid tumor biopsy component.

Areas covered

TEX play a critical role in monitoring cancer presence/progression and in reprograming of anti-tumor effector T cells to producers of EVs with pro-tumor activity. TEX are a subset of circulating EVs. Their separation by immune capture from EVs derived from nonmalignant cells allows for TEX phenotypic/functional assessments. TEX cross-talking with CD3(+) T cells induce the release of CD3(+) small EV (sEV), whose cargo of suppressor proteins resembles that of TEX and further contributes to cancer-induced immune suppression. While TEX recapitulate the genetic/molecular phenotype of tumor cells, CD3(+) sEV might serve as ‘T cell liquid biopsy.’

Expert opinion

Preclinical explorations of the role in cancer body fluids of TEX and CD3(+) sEV as cancer biomarkers suggest that these EV subsets may qualify as liquid tumor biopsy noninvasive components in the near future. Their potential to simultaneously serve as noninvasive liquid tumor biopsy and T cell biopsy remains to be validated in future clinical trials.

KEYWORDS:

• Extracellular vesicles (EVs)
• cancer
• tumor-derived exosomes (TEX)
• CD3(+) small EV
• TEX-reprogrammed T cells
• T cell liquid biopsy

Article highlights

• TEX recapitulate the molecular content of parent tumor cells

• TEX Isolation by immune capture from cancer plasma

• TEX reprogram activated T cells to produce pro-tumor CD3(+) sEV

• Immune-based separation of CD3(+) sEV from EVs in cancer plasma

• TEX and the reprogrammed T-cell secretome in cancer plasma are components of liquid tumor biopsy

• TEX serve as potential cancer biomarkers and CD3(+) sEV as immune biomarkers or liquid T cell biopsy

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

Supported in part by National Institutes of Health grants U01-DE029759 and R01-CA 256068