A new review article highlights the expanding importance of glutamine metabolism in shaping the tumor microenvironment, offering fresh perspectives on how metabolic interactions influence cancer progression and therapeutic response. The work brings together current understanding of how this essential nutrient drives communication between tumor cells and surrounding stromal components, opening new avenues for more effective cancer treatment strategies.
Glutamine is increasingly recognized as a central metabolic fuel that supports tumor growth, survival, and adaptation. Within the tumor microenvironment, it functions not only as an energy source but also as a regulator of cellular behavior. Cancer cells depend on glutamine to sustain proliferation, maintain metabolic flexibility, and fuel key pathways such as the tricarboxylic acid cycle, enabling continued growth even under nutrient-limited conditions.
The article emphasizes the complex interplay between tumor cells and stromal cells, including macrophages, T cells, fibroblasts, and dendritic cells. These interactions create a dynamic ecosystem in which glutamine availability shapes both tumor progression and immune responses. In some contexts, glutamine supports immune cell activity and strengthens anti-tumor defenses, while in others it contributes to immune suppression, allowing tumors to evade detection and persist.
Particular attention is given to cancer-associated fibroblasts and tumor-associated macrophages, which actively participate in metabolic exchange. These cells can generate and supply glutamine to tumor cells, reinforcing an environment that promotes tumor survival, invasion, and treatment resistance. At the same time, metabolic byproducts such as ammonia can impair immune cell function, further contributing to an immunosuppressive microenvironment.
The article also highlights the therapeutic potential of targeting glutamine metabolism. By disrupting glutamine uptake, synthesis, or utilization, emerging strategies aim to weaken tumor growth while enhancing anti-tumor immunity. This approach reflects a broader shift toward therapies that address not only cancer cells but also the surrounding biological environment that sustains them.
Overall, this review underscores metabolic reprogramming as a defining feature of cancer and positions glutamine as a key regulator of tumor–stroma interactions. By advancing understanding of these complex processes, it points toward innovative strategies that may improve outcomes through more precise targeting of the tumor microenvironment.
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Reference
Zizhuo Li, Jiapeng Deng, Hai Wang, Tao Liu, Yuyang Zhou, Pei Ouyang, Xuan Liang, Xian Zhang, Songtao Qi, Yaomin Li, Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies, Genes & Diseases, Volume 13, Issue 3, 2026, 101834, https://doi.org/10.1016/j.gendis.2025.101834

Funding
National Natural Science Foundation of China 82203368
Science and Technology Program of Guangzhou, Guangdong, China 2025A04J5139
President Foundation of Nanfang Hospital, Southern Medical University, Guangdong, China 2023H020
Natural Science Foundation of Guangdong Province, China 2023A1515011775
College Students' Innovative Entrepreneurial Training Plan Program (China) S202312121119