1. Potential Role of Acetylpolyamines in the Prostatic Tumor Microenvironment
- Author
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Cernyar, Brent and Cernyar, Brent
- Abstract
Prostate cancer is the most common cancer in men excluding non-melanoma skin cancer, and the second leading cause of cancer-related mortality after lung cancer. Early stages of prostate cancer are dependent on androgen for proliferation and survival, and can be curable with standard surgical or radiation treatment options. Unfortunately, recurrent and metastatic prostate cancer is highly refractory. Eventually the disease will develop castration resistance which is incurable with our currently available androgen deprivation therapies and chemotherapies. Initially, immunotherapy in preclinical trials showed promise in activating the innate and adaptive immune system to target prostate cancer cells. While sipuleucel-T and pembrolizumab have been approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer patients, immunotherapies have overall shown only modest efficacy in clinical practice. Prostate tumors are heterogeneous and considered an immunologically “cold” tumor due to low expression of neoantigens and low tumor mutational burden, creating a significant obstacle to treatment with immunotherapy. In addition, the prostatic tumor microenvironment secretes factors that recruit an abundance of anti-inflammatory tumor associated macrophages (TAM), increases regulatory T cell infiltration, and activates immature myeloid cell differentiation to myeloid derived suppressor cells. These cells create an immunosuppressive barrier which inactivates cytotoxic T cells and prevents natural killer cell permeability. As of yet, we are unable to explain the abundance of infiltrating tumor associated macrophages associated with metastatic prostate cancer tumors. One factor may be acetylated polyamines released by prostate cancer cells into the tumor microenvironment. Classically, literature reports decreased total intracellular polyamine concentration with prostate cancer progression, suggesting polyamines have ant
- Published
- 2024