Aug 2026· Oncology Report· Vol 56, pp. 1-21· 0 citations· 110 references
Medicine
TL;DR
The glutamine-ammonium axis is highlighted as a promising but largely untapped therapeutic target requiring translation into clinical investigation, including combination strategies with immunotherapy.
Abstract
Prostate cancer progression is typically driven by metabolic reprogramming and immune evasion, yet the interface between these processes remains incompletely understood. Dysregulated glutamine metabolism extends beyond bioenergetic support to actively shape antitumor immunity through nutrient competition and ammonium accumulation within the tumor microenvironment. Ammonium, traditionally viewed as a toxic waste product, is a critical immunosuppressive metabolite that impairs T cell function and promotes macrophage M2 polarization. The present review aimed to summarize the bidirectional crosstalk between tumor metabolism and immune cells, with emphasis on how metabolic alterations drive therapeutic resistance. While the majority of evidence supporting this axis derives from preclinical models, the present review highlights the glutamine-ammonium axis as a promising but largely untapped therapeutic target requiring translation into clinical investigation, including combination strategies with immunotherapy.
Mechanisms underlying the immunosuppressive microenvironment in hepatocellular carcinoma (HCC) extend beyond immune checkpoints to include metabolic competition. Here, we identify a metabolic evasion pathway driven by SLC1A5 overexpression, which enables HCC cells to sequester glutamine from the tumor microenvironmen...
Jingjing Nian, Zi-Ran Wang, Shi-Yi Chen et al.· Cell Death & Disease· 0 citations
Glutamine, the most abundant amino acid in human serum, serves not only as a key nutrient for maintaining normal cellular biological functions but also as an essential metabolic substrate for the proliferation and survival of tumor cells. Tumor cells exhibit a pronounced characteristic of “glutamine addiction” through...
Metabolic reprogramming is a hallmark of tumor initiation and progression. Previous studies have focused mainly on glucose and lipid metabolism, with emphasis on the Warburg effect and de novo lipogenesis. Based on the shift in research paradigms, this review focuses on amino acid metabolism, which has long been overlo...
Xuan-Hao Wu, Xiao-Dan Mao· International Journal of Med...· 0 citations
Glioblastoma (GB) is characterized by aggressive progression and frequent recurrence despite temozolomide (TMZ)-based therapy. Although resistance is commonly linked to DNA repair mechanisms, these pathways do not fully explain tumor persistence under therapeutic stress. Accumulating evidence suggests that metabolic re...
Mehdi Eshraghi, Ivan Iurchenko, Amir Barzegar Behrooz· Biochimica et Biophysica Act...· 0 citations
Metabolic reprogramming is a fundamental regulator of immune cell fate and function in the tumor microenvironment (TME), though the relative contributions of individual metabolic pathways vary across immune cell subsets, tumor types, and disease stages. Competition for nutrients, hypoxia, and the accumulation of immuno...
Yi-Qing Jiang, Yan-Ling Wu, Tian-Lei Ying· Cancer Biome and Targeted Th...· 0 citations
Emerging evidence demonstrates that tumor metabolic reprogramming not only supports tumor-cell proliferation but also promotes the establishment of an immunosuppressive tumor microenvironment (TME) by altering nutrient competition and metabolite accumulation. Therefore, metabolic reprogramming and immune evasion should...
Hai-Lun Wang, Han-Yuan Zhao, Xue-Lu Pu et al.· Frontiers in Oncology· 0 citations
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