Cancer Research and Treatment

Review Article

Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application: Taerim Oh, Minwoo Kim, Gi-Sue Kang, Sung-Joon Ye, Changhoon Choi, Won Park, Michael Hay, Hiroshi Hirata, G-One Ahn; Cancer Res Treat. 2026;58(1):26-47. Published online April 29, 2025; DOI: https://doi.org/10.4143/crt.2025.200

It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

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Original Article

Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue: Yoon Seok Choi, Seok Jin Kim, Dae Sik Kim, Seh Jong Park, Yong Park, Hye Jin Shin, Kwang-Yoon Jung, Seung-Kuk Baek, Bong Kyung Shin, Jung Woo Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; Cancer Res Treat. 2007;39(3):109-115. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.109

Abstract PDF PubReader ePub

Purpose

Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis.

Materials and Methods

The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue.

Results

The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0~90.0%). A high Glut-1 expression (the percentage of positive tumor cells ≥ the median value, 60%) was associated with the location of primary lesion, lymph node metastasis status and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis.

Conclusion

The expression of Glut-1 may be useful for predicting the prognosis and determining the treatment strategy for the management of squamous cell carcinoma of the tongue.

Citations

Citations to this article as recorded by

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