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CD38 in Advanced Prostate Cancers.

Christina Guo1, Mateus Crespo2, Bora Gurel2

  • 1The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK.

European Urology
|March 8, 2021
PubMed
Summary
This summary is machine-generated.

CD38 expression on prostate cancer immune cells is linked to poorer survival. Increased CD38+ tumor-infiltrating immune cells correlate with immunosuppression and worse outcomes in prostate cancer patients.

Keywords:
Adenosine pathwayB lymphocyteCD38Castration-resistant prostate cancerInflammationMyeloid cellPlasmacyteProstate cancerT cell exhaustionTumour microenvironment

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • CD38, an ectoenzyme, contributes to adenosine generation, a mechanism tumors use to evade immune responses.
  • The expression and function of CD38 in prostate cancer (PC) and its tumor-infiltrating immune cells (TIICs) remain largely uncharacterized.

Purpose of the Study:

  • To investigate CD38 expression on prostate cancer epithelial cells and TIICs.
  • To correlate CD38 expression with clinical outcomes in prostate cancer patients.

Main Methods:

  • Analysis of RNA sequencing data from metastatic castration-resistant prostate cancer (mCRPC) cohorts.
  • Immunohistochemical scoring of CD38 expression in castration-sensitive (CSPC) and castration-resistant (CRPC) prostate cancer biopsies.
  • Multiplex immunofluorescence to determine CD38 protein expression on TIICs and epithelial cells.

Main Results:

  • CD38 mRNA expression in mCRPC was associated with upregulated immune signaling, including IL-12, IL-23, IL-27, adenosine signaling, and T cell exhaustion signatures.
  • CD38 protein was predominantly found on diverse TIICs (B cells, myeloid cells) but not on tumor epithelial cells.
  • Density of CD38+ TIICs increased with progression to CRPC and was independently linked to worse overall survival.

Conclusions:

  • CD38+ prostate TIICs are associated with immunosuppressive mechanisms and predict worse survival in prostate cancer.
  • The role of CD38 in prostate cancer progression warrants further investigation for potential therapeutic targeting in advanced disease.