Tumor-derived extracellular vesicles in the colorectal cancer immune environment and immunotherapy

Ajay Prakash, Travis J Gates, Xianda Zhao, Dechen Wangmo, Subbaya Subramanian

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Despite significant advances in the screening, diagnosis, and treatment of colorectal cancer (CRC) immune checkpoint inhibitors (ICIs) continue to have limited utility outside of microsatellite-high disease. Given the durable response to immunotherapy seen across malignancies, increasing CRC response rates to ICI therapy is an active area of clinical research. An increasing body of work has demonstrated that tumor-derived extracellular vesicles (TEVs) are key modulators in tumor signaling and the determinants of the tumor microenvironment. Pre-clinical models have shown that TEVs are directly involved in antigen presentation and are involved in radiation-induced DNA damage signaling. Both direct and indirect modifications of these TEVs can alter CRC immunogenicity and ICI treatment response, making them attractive targets for potential therapeutic development. In addition, modified TEVs can be developed using several different mechanisms, with varied cargo including micro-RNAs and small peptide molecules. Recent work has shown strong pre-clinical evidence of injected modified TEV-induced ICI activity, with knockdown of the micro-RNA miR-424 in TEVs improving CRC immunogenicity and increasing anti-PD-1 activity in mouse models. Clinical trials are ongoing in the evaluation of modified TEVs in cancer therapy, but they appear to be a promising therapeutic target in CRC.

Original languageEnglish (US)
Article number108332
JournalPharmacology and Therapeutics
Volume241
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
SS is supported by research grants funded by the Masonic Cancer Center ChainBreaker Fund, Mezin Koats colorectal cancer, Minnesota Colorectal Cancer Funds, and the research funds from the Department of Surgery and CTSI, University of Minnesota . DW is supported by the National Institutes of Health's National Center for Advancing Translational Sciences , grants TL1R002493 and UL1TR002494 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences. TJG and DW are supported by the Minnesota Colorectal Cancer Research Foundation .

Publisher Copyright:
© 2022

Keywords

  • Colorectal cancer
  • Immunotherapy
  • Tumor-derived extracellular vesicles
  • micro-RNA

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural

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