Interferon stimulated gene 15 (ISG15) in cancer: An update

Cancer Lett. 2023 Mar 1:556:216080. doi: 10.1016/j.canlet.2023.216080. Epub 2023 Feb 1.


Among the plethora of defense mechanisms which a host elicits after pathogen invasion, type 1 interferons play a central role in regulating the immune system's response. They induce several interferon-stimulated genes (ISGs) which play a diverse role once activated. Over the past few decades, there have been several studies exploring the role of ISGs in cancer and ISG15 is among the most studied for its pro and anti-tumorigenic role. In this review, we aim to provide an update on the recent observations and findings related to ISG15 in cancer. We provide a brief overview about the initial observations and important historical findings which helped scientists understand structure and function of ISG15. We aim to provide an overview of ISG15 in cancer with an emphasis on studies which delve into the molecular mechanism of ISG15 in modulating the tumor microenvironment. Further, the dysregulation of ISG15 in cancer and the molecular mechanisms associated with its pro and anti-tumor roles are discussed in respective cancer types. Finally, we discuss multiple therapeutic applications of ISG15 in current cancer therapy.

Keywords: Cancer; Interferon-stimulated gene 15; Type I interferon; Ubiquitin-like protein.

Publication types

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

MeSH terms

  • Cytokines* / genetics
  • Humans
  • Interferon Type I / genetics
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Tumor Microenvironment
  • Ubiquitins* / genetics


  • Cytokines
  • Interferon Type I
  • ISG15 protein, human
  • Ubiquitins