Molecular Oncology (Oct 2024)

Immune evasion: An imperative and consequence of MYC deregulation

  • Bastian Krenz,
  • Jongkuen Lee,
  • Toshitha Kannan,
  • Martin Eilers

DOI
https://doi.org/10.1002/1878-0261.13695
Journal volume & issue
Vol. 18, no. 10
pp. 2338 – 2355

Abstract

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MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC's function from being a gene‐specific transcription factor to an essential stress resilience factor. In highly proliferating cells, MYC preserves cell integrity by promoting DNA repair at core promoters, protecting stalled replication forks, and/or preventing transcription‐replication conflicts. Furthermore, an increasing body of evidence demonstrates that MYC not only promotes tumorigenesis by driving cell‐autonomous growth, but also enables tumors to evade the host's immune system. In this review, we summarize our current understanding of how MYC impairs antitumor immunity and why this function is evolutionarily hard‐wired to the biology of the MYC protein family. We show why the cell‐autonomous and immune evasive functions of MYC are mutually dependent and discuss ways to target MYC proteins in cancer therapy.

Keywords