The potential role of tumor-derived exosomes in diagnosis, prognosis, and response to therapy in cancer

ABSTRACT

Introduction

Small extracellular vesicles (sEV) produced by tumors and called TEX mediate communication and regulate the tumor microenvironment. As a ‘liquid tumor biopsy’ and with the ability to induce pro-tumor reprogramming, TEX offer a promising approach to monitoring cancer progression or response to therapy.

Areas covered

TEX isolation from body fluids and separation by immunoaffinity capture from other EVs enables TEX molecular and functional characterization in vitro and in vivo. TEX carry membrane-bound PD-L1 and a rich cargo of other proteins and nucleic acids that reflect the tumor content and activity. TEX transfer this cargo to recipient cells, activating various molecular pathways and inducing pro-tumor transcriptional changes. TEX may interfere with immune therapies, and TEX plasma levels correlate with patients’ responses to therapy. TEX induce local and systemic alterations in immune cells which may have a prognostic value.

Expert opinion

TEX have a special advantage as potential cancer biomarkers. Their cargo emerges as a correlate of developing or progressing malignant disease; their phenotype mimics that of the tumor; and their functional reprogramming of immune cells provides a reading of the patients’ immune status prior and post immunotherapy. Validation of TEX and T-cell-derived sEV as cancer biomarkers is an impending future task.

KEYWORDS:

• Cancer biomarkers
• prognosis
• response to therapy
• small extracellular vesicles (sEV)
• tumor-derived exosomes (TEX)

Article highlights

• Tumor-derived exosomes (TEX) originate from the endocytic compartment of tumor cells and mimic the molecular content of parental cells.

• TEX are present in all body fluids of cancer patients at levels that change with disease progression/regression.

• TEX are enriched in immunosuppressive proteins, including PD-L1, and suppress functions of immune effector cells in vitro and in vivo.

• Phenotypic and functional profiles of TEX have prognostic/diagnostic significance in cancer, but their role as ‘liquid biopsy’ requires further clinical validation.

This box summarizes the key points contained in the article.

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.

Reviewer disclosures

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

Additional information

Funding

The work was supported in part by NIH grants R01 CA168626, U01 DE029759 and SBIR 75N91019C00042 to TL Whiteside and by NCN (National Science Center, Poland) grant OPUS 14 2017/27/B/NZ6/01990 and NAWA grant PPI/APM/2019/1/00051/U001 to Narodowe Centrum Nauki.