Prostate cancer progression is commonly associated with changes in cellular metabolism and concurrent mechanisms that allow tumors to evade immune control. The review by Wang et al. frames these processes as an interdependent metabolic–immune crosstalk within the tumor microenvironment. The authors emphasize that metabolic reprogramming in cancer cells not only meets bioenergetic and biosynthetic demands but also actively modulates antitumor immunity.
Clinical and preclinical literature summarized in the review support a model in which nutrient availability, metabolic byproducts, and cell-intrinsic metabolic pathways influence immune cell phenotype and function. The review highlights that understanding this interface is key to addressing therapeutic resistance in prostate cancer.
The authors focus on glutamine metabolism as a central node linking tumor metabolic activity to immune modulation. Beyond serving as a carbon and nitrogen source for proliferating tumor cells, glutamine metabolism creates competitive microenvironmental conditions that can deprive immune cells of critical nutrients. This nutrient competition is presented as a mechanism by which tumors restrict effective antitumor immune responses.
Wang et al. describe glutamine's role in supporting tumor growth while altering immune cell behavior through metabolic competition and downstream metabolites. The review frames glutamine metabolism as a bidirectional communicator: tumor cells use glutamine to support malignant processes and, in doing so, create metabolic states that impair immune surveillance.
A central point of the review is the re-evaluation of ammonium (ammonia) within the tumor microenvironment. Historically treated as a toxic waste product of nitrogen metabolism, ammonium is highlighted here as a biologically active metabolite with immunosuppressive effects. The authors summarize evidence indicating that ammonium accumulation can:
This reframing positions ammonium not only as a metabolic byproduct but as a potential mediator of immune escape in prostate cancer.
The review links metabolic reprogramming, including glutamine utilization and ammonium production, to mechanisms of therapeutic resistance. By shaping immune cell composition and function in the tumor microenvironment, these metabolic alterations can undermine responses to treatments that rely on immune activity, including immunotherapies.
Wang et al. underscore that metabolic changes contribute to a microenvironment less permissive to immune-mediated tumor control, thereby facilitating tumor escape and limiting therapeutic efficacy. The authors report that much of the supporting data come from preclinical studies rather than clinical trials.
Based on the summarized evidence, the review argues that the glutamine–ammonium axis represents a promising but underexplored therapeutic target in prostate cancer. The authors call for clinical translation of preclinical findings and suggest that strategies targeting glutamine metabolism or ammonium signaling should be evaluated in combination with immunotherapy.
The review notes that the bulk of evidence at present derives from experimental models. Consequently, the authors emphasize the need for clinical investigation to determine whether targeting this metabolic axis can enhance antitumor immunity and overcome treatment resistance in patients.
Wang et al. conclude that metabolic reprogramming and immune evasion are tightly interconnected in prostate cancer, with glutamine metabolism and ammonium acting as pivotal components of this crosstalk. They present the glutamine–ammonium axis as a research priority and a candidate therapeutic target, while acknowledging that translation to clinical practice remains limited by the predominance of preclinical data.
The review calls for focused clinical research to validate the immunomodulatory role of these metabolic pathways in humans and to develop combination treatment strategies that incorporate metabolic modulation with immunotherapeutic approaches.
Notes
(Details such as specific experimental results, quantitative data, or clinical trial outcomes were not reported in the PubMed abstract and are therefore not described here.)