The role of extracellular vesicles in immune cell exhaustion and resistance to immunotherapy

ABSTRACT

Introduction

Extracellular vesicles (EVs) are membrane-bound nanoparticles for intercellular communication. Subtypes of EVs, namely exosomes and microvesicles transfer diverse, bioactive cargo to their target cells and eventually interfere with immune responses. Despite being a promising approach, cancer immunotherapy currently faces several challenges including immune resistance. EVs secreted from various sources in the tumor microenvironment provoke immune cell exhaustion and lower the efficacy of immunological treatments, such as CAR T cells and immune checkpoint inhibitors.

Areas covered

This article goes through the mechanisms of action of various types of EVs in inhibiting immune response and immunotherapies, and provides a comprehensive review of EV-based treatments.

Expert opinion

By making use of the distinctive features of EVs, natural or modified EVs are innovatively utilized as novel cancer therapeutics. They are occasionally coupled with currently established treatments to overcome their inadequacies. Investigating the properties and interactions of EVs and EV-based treatments is crucial for determining future steps in cancer therapeutics.

GRAPHICAL ABSTRACT

KEYWORDS:

• Exosomes
• Extracellular vesicles
• Immunotherapy
• T-cell exhaustion
• Nanoparticles

Article highlights

• Among the distinctive mechanisms of immune evasion utilized by cancers, immune exhaustion remains a considerable challenge in applying anti-cancer therapeutics.

• Extracellular vesicles (EVs) secreted from various sources provide a means of intercellular communication contributing to immune cell exhaustion and pro-tumor functions.

• EVs may carry immunosuppressive cargos, contain inhibitory cytokines, promote inhibitory phenotypes in cells, induce immune cell apoptosis, and undermine T cell signaling cascades.

• EVs vigorously inhibit immunotherapies such as CAR T cells or immune checkpoint inhibitors.

• The unique characteristics of EVs are taken advantage of in order to generate novel cancer vaccines, as well as other EV-based therapeutics.

• EV mimetics and engineered EVS can be used in combination with other anti-cancer agents to enhance their efficacy.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Acknowledgments

The authors used some features from Servier Medical Art (https://smart.servier.com/) , under a Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/) , to design the figures and the graphical abstract of the article.

Additional information

Funding

This paper was not funded.