Exosomes in the tumor microenvironment as mediators of cancer therapy resistance

Mol Cancer. 2019 Mar 1;18(1):32. doi: 10.1186/s12943-019-0975-5.

Abstract

Exosomes are small extracellular vesicles that contain genetic material, proteins, and lipids. They function as potent signaling molecules between cancer cells and the surrounding cells that comprise the tumor microenvironment (TME). Exosomes derived from both tumor and stromal cells have been implicated in all stages of cancer progression and play an important role in therapy resistance. Moreover, due to their nature as mediators of cell-cell communication, they are integral to TME-dependent therapy resistance. In this review, we discuss current exosome isolation and profiling techniques and their role in TME interactions and therapy resistance. We also explore emerging clinical applications of both exosomes as biomarkers, direct therapeutic targets, and engineered nanocarriers. In order to fully understand the TME, careful interrogation of exosomes and their cargo is critical. This understanding is a promising avenue for the development of effective clinical applications.

Keywords: Biomarkers; Exosomes; Therapy resistance; Tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antibodies, Neutralizing / pharmacology
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / immunology*
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • Cancer-Associated Fibroblasts / drug effects
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / pathology
  • Cell Communication / immunology
  • Disease Progression
  • Drug Carriers
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / immunology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / pathology
  • Exosomes / chemistry
  • Exosomes / immunology*
  • Exosomes / transplantation
  • Humans
  • Immunotherapy / methods
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Stromal Cells / drug effects
  • Stromal Cells / immunology
  • Stromal Cells / pathology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Antibodies, Neutralizing
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Drug Carriers