Signaling new therapeutic opportunities: cytokines in prostate cancer.

Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes. These efforts include studies with anti-PD1/PD-L1 and anti-CTLA-4 alone and in combination with existing standards of care. These strategies are generally T-cell centric and disregard the broader complex and pleiotropic components of the prostate cancer tumor microenvironment such as natural killer cells, myeloid-derived suppressor cells, and tumor-associated macrophages. We performed an online literature search and undertook a review of existing preclinical and clinical literature for cytokine-based therapy related to prostate cancer, specifically on interleukin (IL)-2, IL-15, IL-12, IL-23, IL-8, and transforming growth factor (TGF)-β. Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations, which may play more important roles in the prostate cancer tumor microenvironment.