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Combining immune checkpoint blockade with myeloid-derived suppressor cell targeted therapy shows promise for treating metastatic castration-resistant prostate cancer (mCRPC). This novel approach overcomes resistance and enhances anti-tumor responses in mCRPC.

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Area of Science:

  • Oncology
  • Immunology
  • Cancer Therapy

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) often progresses despite androgen deprivation therapy.
  • Immune checkpoint blockade (ICB) shows efficacy in various cancers but faces resistance in mCRPC.
  • Myeloid-derived suppressor cells (MDSCs) contribute to tumor immune evasion and prostate cancer progression.

Purpose of the Study:

  • To investigate the efficacy of combining ICB with MDSC-targeted therapy in mCRPC.
  • To develop a novel chimeric mouse model for testing combination therapies in an autochthonous setting.

Main Methods:

  • Developed a novel chimeric mouse model of mCRPC.
  • Tested combination therapy of anti-CTLA4 and anti-PD1 (ICB) with MDSC-targeted agents (cabozantinib, BEZ235).
  • Assessed anti-tumor activity and elucidated underlying mechanisms.

Main Results:

  • Combination ICB and MDSC-targeted therapy demonstrated robust synergistic anti-tumor responses in mCRPC.
  • Monotherapy with ICB or MDSC-targeted agents showed minimal efficacy.
  • Combination therapy led to upregulation of interleukin-1 receptor antagonist and suppressed MDSC-promoting cytokines.

Conclusions:

  • Combining ICB with MDSC-targeted therapy offers a promising strategy to overcome resistance and enhance treatment efficacy in mCRPC.
  • This approach warrants further clinical investigation for mCRPC treatment.