Cancer Res Treat.
2026 Jan;58(1):26-47. 10.4143/crt.2025.200.
Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application
- Affiliations
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- 1College of Veterinary Medicine, Seoul National University, Seoul, Korea
- 2Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Korea
- 3Department of Radiation Oncology, Samsung Medical Center, Seoul, Korea
- 4Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand
- 5Division of Bioengineering and Bioinformatics, Faculty of Information Science and Technology, Hokkaido University, Sapporo, Japan
- 6Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
- KMID: 2575806
- DOI: http://doi.org/10.4143/crt.2025.200
Abstract
- 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.
