The tumor microenvironment (TME) plays a pivotal role in shaping immunometabolism in prostate cancer, influencing disease progression and therapeutic response. This review examines the dynamic interactions between tumor cells and immune cells within the prostate cancer TME, focusing on how metabolic reprogramming of both tumor and immune cells drives immunosuppression. Key immune players, including T-cells, macrophages, and myeloid-derived suppressor cells, undergo metabolic adaptations influenced by hypoxia, nutrient deprivation, and signaling from tumor cells. Additionally, we discuss the metabolic pathways involved, such as glycolysis and oxidative phosphorylation, and how these processes are exploited by cancer cells to evade immune surveillance. Furthermore, this review highlights potential therapeutic strategies targeting immunometabolism, including metabolic inhibitors and their combination with immunotherapies. A deeper understanding of the complex role of immunometabolism in prostate cancer will not only provide insights into the tumor’s immune evasion mechanisms but also facilitate the development of novel treatment approaches that enhance the efficacy of current therapies.

The cyclic GMPAMP synthase (cGAS) stimulator of interferon genes (STING) pathway is a central component of innate immunity that links cytosolic DNA sensing to type I interferon and NF-κB-driven inflammatory responses. Although transient STING stimulation facilitates antimicrobial defense, tissue remodeling, and tumor immunosurveillance, sustained or maladjusted signaling facilitates chronic sterile inflammation, fibrosis, immune impairment, and carcinogenesis. Mitochondrial injury, cellular senescence, infection-related stress, and DNA damage are caused by STING in epithelial-rich organs like the kidney and prostate, which can cause inflammatory diseases and context-dependent immunomodulation in cancer. This mini-review provides an integrated view of STING activation in renal and prostate tissues, elucidating common mechanistic activators, distinct pathological outcomes, and new translational possibilities. Most recent therapeutic strategies, such as STING agonists to promote antitumor immunity and STING inhibitors to reduce maladaptive inflammation. Further insight into cell-specific and disease-stage-dependent STING regulation will be critical for developing safe and effective interventions to achieve immune homeostasis in renal and prostate pathologies.