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Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression

Duminduni Hewa Angappulige1, Nupam P Mahajan2, Kiran Mahajan2

  • 1Division of Urologic Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA.

Trends in Cancer
|February 10, 2024
PubMed

Insights

Prostate cancer (PC) becomes resistant to treatment due to epigenetic changes that suppress the immune system. Targeting these epigenetic regulators may help overcome treatment resistance in PC.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics

Background:

  • Prostate cancer (PC) is characterized by an immunosuppressive tumor microenvironment (TME).
  • Androgen receptor (AR) antagonism leads to myeloid-derived suppressor cells (MDSCs), senescent neutrophils, and T cell exhaustion in the TME.
  • Castration-resistant PC (CRPC) is associated with specific epigenetic modifications.

Purpose of the Study:

  • To review the role of de novo epigenetic alterations in driving resistance in prostate cancer.
  • To discuss how targeting epigenetic regulators can overcome immune suppression in PC.

Main Methods:

  • Review of existing literature on epigenetic modifications in prostate cancer.
  • Analysis of de novo post-translational acetylation and phosphorylation events.
  • Examination of the integration of chromatin changes into cellular processes.

Main Results:

  • De novo acetylation of AR, HOXB13, and H2A, and phosphorylation of H4 are key epigenetic events in CRPC.
  • These epigenetic changes are integrated via phosphorylation of AR, ACK1, ATPF1A, and SREBP1.
  • Epigenetic alterations contribute to immune suppression and treatment resistance in PC.

Conclusions:

  • De novo epigenetic alterations are crucial drivers of resistance in prostate cancer.
  • Targeting these epigenetic regulators presents a potential strategy to overcome immune suppression and enhance immunotherapy efficacy in PC.
Keywords:
chromatinepigeneticsimmune suppressionprostate cancertestosterone

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