Long-lasting immune challenges such as chronic inflammation or chronic illness such as cancer, results in abnormally high exhaustion rates of immune cells that ultimately lead to their death. Recently, Scharping et al. (2021)1 demonstrated that immune cell exhaustion was caused by mitochondrial dysfunction associated with increased reactive oxygen species, such as the hydroxyl radical. Interestingly, Chen et al. (2020)2 demonstrated that just two weeks of molecular hydrogen inhalation could reactivate normal levels of exhausted immune cells in stage III and IV cancer patients.
At the start of the study, the patient presented with abnormally high levels of exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells, and abnormally low level of functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After two weeks of molecular hydrogen inhalation, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. All the while, T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells subsets increased to within the normal range.
This suggests that the scavenging of the hydroxyl radical may be able to restore the normal function of the immune system, by rescuing the abnormal exhaustion of its effector cells.
- Scharping, N. E. et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol 22, 205–215 (2021).
- Chen, J.-B. et al. Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study. Medical Gas Res 10, 149 (2020).