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Inhibiting exosomal MIC-A and MIC-B shedding of cancer cells to overcome immune escape: new insight of approved drugs

  • Milad Moloudizargari
  • Mohammad Hossein Asghari
  • Esmaeil MortazEmail author
Short communication

Abstract

Our knowledge of the role of innate immunity in protecting against cancers has expanded greatly in recent years. An early focus was on the adoptive transfer of natural killer (NK) cells and, although this approach has demonstrated promising results in many patients, a few limitations including immune escape of tumors from cytotoxic killing by NK cells have caused treatment failures. Downregulation of the expression of activating ligands on the surface of cancer cells and prevention of the activity of soluble factors are among the mechanisms employed by cancer cells to overcome NK-mediated immunity. It has become evident that a class of small membranous structures of endosomal origin known as exosomes play a key role in regulating the local tumor microenvironment. Here we hypothesize that exosome secretion by cancer cells, which is greater than that of normal cells, is an important escape mechanism employed by cancer cells. Interruption of exosome release by various inhibitory agents in combination with the adoptive transfer of NK cells may overcome, at least in part, the treatment failures that occur with adoptive NK cell transfer. In this regard, repositioning of approved drugs with previously shown effects on exosome release may be a good strategy to bypass the safety issues of newly identified agents and will also dramatically reduce the huge costs of drug approval process.

Notes

Acknowledgements

This article has been extracted from the thesis written by Mr. Milad Moloudizargari in School of Medicine Shahid Beheshti University of Medical Sciences. (Registration No: 260). Ethics committee approval ID: IR.SBMU.MSP.REC.1397.578.

Compliance with ethical standards

The authors have no conflicts of interest to declare. This research is based on a review of the literature and involves no animal/human experiments.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Immunology, School of Medicine, Student Research CommitteeShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Pharmacology, School of MedicineBabol University of Medical SciencesBabolIran
  3. 3.Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran

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