[Okayama University] Rebooting Dormant Abilities with 'Pseudo-Hypoxia' ~Simultaneous Awakening of Immunity and Repair Power Driven by Iron Mobilizing Chelators~

Press release on joint research results from Okayama University and Toyama University.

March 29, 2026 National University Corporation Okayama University https://www.okayama-u.ac.jp/

・We have elucidated the molecular mechanism by which specific 'iron mobilizing iron chelators' block the function of cellular oxygen sensor enzymes, inducing a state of 'functional pseudo-hypoxia' where cells mistakenly perceive a lack of oxygen even in an environment with sufficient oxygen.

・When this 'false hypoxia alarm' sounds, the cell's emergency switch is turned on, simultaneously releasing and rebooting the body's own powerful 'immunity (anti-tumor effects)' and 'tissue repair capabilities (nerve regeneration)' that were previously dormant.

・This method has shown potential to improve the therapeutic effects for colorectal and lung cancers, which are resistant to existing immunotherapies. Furthermore, in aged mouse models, it has demonstrated the possibility of suppressing the decline in cognitive function (working memory) without causing inflammation in the brain. This holds promise as a completely new platform therapeutic concept for intractable diseases.

◆Overview A joint research team, including Associate Professor Toshiaki Ohara and Professor Akihiro Matsukawa from the Department of Pathology (Immunopathology), Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University; Lecturer Kazuhiro Noma from the Department of Clinical Medicine (Gastroenterological Surgery), Faculty of Medicine; Associate Professor Hodaka Kawai from the Department of Oral Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University; Professor Yoshiaki Iwasaki from the Department of Management of Research and Educational Development, Okayama University; Professor Toru Yamashita from the Department of Neurology, Faculty of Medicine, Toyama University; and Associate Professor Tomonari Kasai from the Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, has revealed that by artificially inducing 'functional pseudo-hypoxia' using iron mobilizing iron chelators, the dormant immune and repair capabilities within the body can be dramatically enhanced, leading to the augmentation of anti-tumor immune responses against cancer and the suppression of cognitive decline.

The research team orally administered iron mobilizing iron chelators (such as Roxadustat and SP10) to mouse models of colorectal and lung cancer to induce pseudo-hypoxia.

As a result, the secretion of a key cytokine that activates immune cells (IL-2) was promoted, and the efficacy of existing immune checkpoint inhibitors (anti-PD-1 antibody) was synergistically enhanced.

Furthermore, when the same method was applied to aged mice, it was confirmed that nerve regeneration signals were selectively activated without causing harmful inflammation in the brain, suppressing the decline in working memory associated with aging.

The utilization of the new concept of 'functional pseudo-hypoxia' has the potential to develop into next-generation innovative therapies for intractable modern diseases such as cancer and dementia, not by attacking the diseases from the outside, but by maximizing the inherent strengths of the body to confront them.

These findings have been published in three international academic journals.

This information was released by Okayama University on March 26, 2026.

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