Overcoming Immune Evasion in the Prostate Tumor Microenvironment: Novel Targeted Strategies to Improve Treatment...

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Prostate cancer, despite therapeutic advances, remains a significant cause of male mortality.
• Metastatic castration-resistant prostate cancer (mCRPC) eventually develops in most patients, indicating treatment limitations.
• The tumor microenvironment (TME) is increasingly recognized as a critical factor in immune evasion and treatment resistance in mCRPC.

Purpose of the Study:

• To review the current understanding of immune suppression within the prostate tumor microenvironment (TME).
• To explore cellular and molecular components of the TME that drive therapeutic resistance and disease progression.
• To examine emerging therapeutic strategies targeting the TME and combination approaches for mCRPC.

Main Methods:

• Literature review of current knowledge on prostate cancer TME.
• Analysis of immune suppressive cells (e.g., cancer-associated fibroblasts, myeloid-derived suppressor cells, tumor-associated macrophages).
• Examination of immune checkpoint pathways and metabolic alterations within the TME.

Main Results:

• The prostate TME contains various cellular and molecular components that promote immune suppression.
• These components, including specific cell types and metabolic pathways, contribute to resistance against therapies.
• The TME's role in immune evasion and therapeutic failure is a key factor in mCRPC progression.

Conclusions:

• Targeting the immune suppressive networks within the prostate TME presents potential therapeutic opportunities.
• Emerging strategies focus on reprogramming the TME and combining immunotherapies with other inhibitors.
• Future mCRPC treatment success relies on rational combinations addressing tumor-intrinsic resistance and TME-mediated immune suppression, guided by biomarkers.