GLUT1 Antibodies: How Do They Become Key to Enhancing Anti-Tumor Immune Responses?

I. How Do Tumor Cells Evade Immune Surveillance Through Metabolic Reprogramming?
 
Tumor cells establish an immune-tolerant microenvironment through metabolic reprogramming, which is a crucial mechanism for evading immune surveillance. Abnormal glucose metabolism is a core feature of tumor metabolic reprogramming. Studies show that tumor cells highly express Glucose Transporter 1 (GLUT1), acquiring energy through enhanced glycolysis while creating a microenvironment conducive to immune escape. This metabolic characteristic not only provides the material basis for rapid tumor cell proliferation but also affects immune cell function by regulating cytokine signaling pathways.

In the tumor microenvironment, cytotoxic T lymphocytes (CTLs) are the primary anti-tumor effector cells, killing tumor cells through mediators like granzymes, interferon-gamma, and tumor necrosis factor-alpha (TNF-α). However, tumor cells upregulate GLUT1 expression to enhance glycolytic activity, potentially altering their sensitivity to T cell-mediated killing—a mechanism not yet fully understood. Deepening our understanding of the interaction between tumor metabolism and immune responses is highly significant for developing novel immunotherapy strategies.

 
II. What are the Differences in GLUT1 Expression Patterns Between Tumor and Immune Cells?
 
Single-cell transcriptome analysis reveals differential expression patterns of GLUT1 in tumor versus immune cells. In tumor cells, GLUT1 encoded by the SLC2A1 gene is highly expressed, while in T cells, GLUT3 encoded by the SLC2A3 gene is predominantly expressed. This differential expression pattern provides a theoretical basis for selectively targeting tumor cells.
Validation via RNA sequencing data confirms that GLUT1 expression levels are significantly higher than GLUT3 in tumor cells, whereas activated T cells show the opposite pattern. This tissue-specific expression difference suggests that targeting GLUT1 might selectively affect tumor cell metabolism without significantly interfering with T cell glucose uptake and function. This finding provides important evidence for developing immune therapy strategies targeting tumor metabolism.
 
III. How Does GLUT1 Regulate Tumor Cell Sensitivity to TNF-α-Mediated Killing?
 
Mechanistic studies indicate that GLUT1 participates in immune escape by regulating tumor cell sensitivity to TNF-α-induced apoptosis. When using the GLUT1 inhibitor BAY-876 or downregulating GLUT1 expression via gene knockout technology, tumor cell sensitivity to TNF-α-mediated killing in T cell-conditioned medium is significantly enhanced. This effect is particularly evident in Transwell co-culture systems, confirming its dependence on soluble factors rather than direct cell contact.

Further research found that GLUT1 inhibition leads to tumor cell metabolic reprogramming, manifested as decreased glycolysis and enhanced oxidative phosphorylation, subsequently increasing intracellular reactive oxygen species (ROS) levels. ROS accumulation downregulates c-FLIP expression, a key inhibitory protein in the TNF-α-induced apoptosis pathway. The downregulation of c-FLIP promotes the activation of the caspase-8-dependent apoptotic pathway, thereby enhancing tumor cell sensitivity to TNF-α-mediated killing.
 
IV. How Does GLUT1 Targeting Affect Anti-Tumor Immunity in In Vivo Models?
In animal models, GLUT1-knockout tumor cells show significantly restricted growth in immunocompetent mice but grow unaffected in immunodeficient NSG mice, indicating that GLUT1 deletion-induced tumor suppression depends on an intact immune system. Analysis of tumor-infiltrating lymphocytes reveals significantly increased numbers of CD8+ T cells, CD4+ T cells, and NK cells in GLUT1-knockout tumors, indicating an improved immune microenvironment.

Mixed tumor cell transplantation experiments further confirmed that GLUT1-knockout tumor cells are selectively eliminated in immunocompetent hosts, and this effect depends on the TNF-α receptor signaling pathway. When the TNF-α receptor is simultaneously knocked out, the growth inhibition phenotype of GLUT1-knockout tumor cells is completely reversed, further confirming the central role of TNF-α in this process.
 
V. How Do GLUT1 Inhibitors Enhance Immunotherapy Efficacy?
The small molecule GLUT1 inhibitor BAY-876 shows good anti-tumor activity in preclinical models. In immunocompetent mouse models, BAY-876 monotherapy significantly inhibits tumor growth, with even more pronounced effects when combined with anti-PD-1 antibodies. However, in immunodeficient mice or TNF-α receptor knockout models, BAY-876's anti-tumor effect completely disappears, indicating its dependence on an intact immune system and TNF-α signaling pathway.

Analysis of tumor-infiltrating immune cells shows that BAY-876 treatment significantly increases the infiltration of CD45+ immune cells, CD8+ T cells, and NK cells, while modulating the immunosuppressive microenvironment. Notably, BAY-876 shows no significant toxic effects on immune cell numbers, consistent with the differential expression pattern of GLUT1 in tumor versus immune cells.
 
VI. What is the Association Between GLUT1 Expression and Clinical Prognosis?
Analysis of clinical cohort data reveals a significant correlation between GLUT1 expression and patient prognosis. In samples from multiple tumor types, high GLUT1 expression negatively correlates with the degree of immune cell infiltration, suggesting GLUT1 might serve as a biomarker for an immunosuppressive microenvironment. Analysis of immune checkpoint inhibitor treatment cohorts found that patients with low glycolytic pathway activity respond better to treatment.

Further analysis shows that TNF-α expression levels in the tumor microenvironment are closely related to patient survival benefit, but this association is significantly influenced by GLUT1 expression levels. In patients with low GLUT1 expression, high TNF-α levels correlate with significant survival advantage; whereas in patients with high GLUT1 expression, the prognostic value of TNF-α is markedly reduced. These clinical data support GLUT1's role as a key regulator of TNF-α-mediated anti-tumor immunity.
 
VII. Which Companies Supply GLUT1 Antibodies?
Hangzhou Start Biotech Co., Ltd. has independently developed the "GLUT1 Recombinant Rabbit Monoclonal Antibody" (Product Name: GLUT1 Recombinant Rabbit mAb (SDT-R057), Product Code: S0B2100). This is a high-performance antibody product characterized by high specificity, excellent sensitivity, and exceptional staining consistency. Developed using recombinant rabbit monoclonal antibody technology and rigorously validated across multiple platforms including Immunohistochemistry and Western Blot, it holds significant application value in energy metabolism research, blood-brain barrier function assessment, and tumor diagnosis.

Core Product Advantages:
* High Specificity and Clear Membrane Localization: This product accurately recognizes Glucose Transporter 1 (GLUT1), demonstrating exceptional cell membrane-specific staining in Formalin-Fixed Paraffin-Embedded samples, with clear signals and low background, providing a reliable basis for accurate interpretation.
* Excellent Staining Stability and Batch Consistency: Under stringent quality control standards, the product exhibits outstanding staining stability and minimal batch-to-batch variation, ensuring reliable and reproducible results under different experimental conditions, providing stable support for clinical diagnosis and basic research.
* Suitable for Various Key Application Scenarios: This product is an ideal tool for the following research areas:
Tumor Metabolism and Diagnostic Research: Serves as a key marker for cellular glucose metabolism, used in studying the Warburg effect in various tumors and for auxiliary diagnosis of malignant mesothelioma, hemangioma, etc.
Blood-Brain Barrier Function Research: For assessing cerebrovascular endothelial cells and the structural and functional integrity of the blood-brain barrier.
Research on Erythrocyte and Blood-Brain Barrier Related Diseases: For mechanistic research and auxiliary diagnosis of diseases like GLUT1 deficiency syndrome.
Exploration of Cellular Energy Metabolism Mechanisms: For basic research exploring cellular glucose uptake and related signaling pathways.

* ​Professional Technical Support: We provide detailed product technical documentation, including complete IHC experimental procedures, optimized antigen retrieval protocols, and clear interpretation standards, fully committed to assisting customers in obtaining accurate and reliable results in metabolic research and tumor pathology diagnosis.

Hangzhou Start Biotech Co., Ltd. is consistently dedicated to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about the "GLUT1 Recombinant Rabbit Monoclonal Antibody" (Product Code S0B2100) or to request a sample test, please feel free to contact us.

Product Information

S0B0127	GLUT-1 Recombinant Rabbit mAb (Alexa Fluor® 488 Conjugate) (SDT-047-53)	Host : Rabbit Conjugation : Alexa Fluor® 488
S0B0123	GLUT-1 Recombinant Rabbit mAb (Alexa Fluor® 594 Conjugate) (SDT-047-53)	Host : Rabbit Conjugation : Alexa Fluor® 594
S0B2102P	S-RMab® GLUT1 Recombinant Rabbit mAb,PBS Only (SDT-047-53)	Host : Rabbit
S0B2102	S-RMab® GLUT1 Recombinant Rabbit mAb (SDT-047-53)	Host : Rabbit
S0B2100P	GLUT1 Recombinant Rabbit mAb,PBS Only (SDT-R057)	Host : Rabbit
S0B2100	GLUT1 Recombinant Rabbit mAb (SDT-R057)	Host : Rabbit