ArticleInternational journal of gynecological cancer : official journal of the International Gynecological Cancer Society2024
Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer.
Article in International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- The role of extracellular vesicles in the communication between endometrial cancer cells and tumour-associated macrophages: a review.Journal of cancer research and clinical oncology · 2025Review
- Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes.Biomedicines · 2025Article
- The potential impact of GLS and PDHA1 on tumor immunity and immunotherapy response in LUSC.Frontiers in genetics · 2025Article
- The immune microenvironment in endometrial carcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2025Review
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Authors and funding
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Funding
Abstract
objectiveIncreased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but also enhance tumor-specific immunity. We investigated the relationship between glutaminase expression, the immune tumor microenvironment, and clinicopathologic features in endometrial cancer.
methodsTissue microarrays constructed from 87 primary endometrial cancer specimens were stained by immunohistochemistry for glutaminase, c-Myc, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), postmeiotic segregation increased 2 (PMS2), estrogen receptor (ER), progresterone receptor (PR), CD8, FoxP3, CD68, programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). We compared the immune tumor microenvironment and clinicopathologic features between glutaminase-high (H-score≥median) versus glutaminase-low (H-score<median) endometrial cancers. We also evaluated data from The Cancer Genome Atlas (TCGA) for 527 endometrial cancer patients in whom RNA-Seq for glutaminase expression was performed and compared long-term clinical outcomes between glutaminase-high (RNA-Seq Z-score≥median) versus glutaminase-low (RNA-Seq score<median) patients.
resultsIn the tissue microarray analysis, glutaminase expression was positively correlated with c-Myc expression (r=0.4226, p<0.0001). Glutaminase-high endometrial cancers were associated with non-endometrioid histology (p=0.0001), high histologic grade (p=0.0004), myometrial invasion (p=0.017), advanced stage (p=0.012), increased FoxP3
conclusionsOur findings indicate that increased glutaminase expression is associated with an immune-suppressive tumor microenvironment, poor clinicopathologic features, and worse long-term outcomes in patients with endometrial cancer.
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