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

Abstract

Following standard treatments, the traditional model for enhancing anti-tumor immunity involves performing immune reconstitution (e.g., adoptive immune cell therapies or immunoenhancing drugs) to prevent recurrence. For patients with advanced non-small cell lung cancer, we report here on two objectives, the immunosenescence for advanced non-small cell lung cancer and hydrogen gas inhalation for immune reconstitution. From July 1 st to September 25 th , 2019, 20 non-small cell lung cancer patients were enrolled to evaluate the immunosenescence of peripheral blood lymphocyte subsets, including T cell, natural killer/natural killer T cell and gamma delta T cell. Two weeks of hydrogen inhalation was performed during the waiting period for treatment-related examination. All patients inhaled a mixture of hydrogen (66.7%) and oxygen (33.3%) with a gas flow rate of 3 L/min for 4 hours each day. None of the patients received any standard treatment during the hydrogen inhalation period. After pretreatment testing, major indexes of immunosenescence were observed. The abnormally higher indexes included exhausted cytotoxic T cells, senescent cytotoxic T cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent cytotoxic T cells decreased to within the normal range, and there was an increase in killer Vδ1 cells. The abnormally lower indexes included functional helper and cytotoxic T cells, Th1, total natural killer T cells, natural killer, and Vδ2 cells. After 2 weeks of hydrogen therapy, all six cell subsets increased to within the normal range. The current data indicate that the immunosenescence of advanced non-small cell lung cancer involves nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment can significantly improve most of these indexes. The study was approved by the Ethics Committee of Fuda Cancer Hospital, Jinan University in China (approval No. Fuda20181207) on December 7 th , 2018, and was registered on ClinicalTrials.gov (ID: NCT03818347) on January 24 th , 2019.

High-flow hydrogen inhalation might suppresses the immune function of middle-aged participants: a self-controlled study

“…For advanced NSCLC patients, the immune senescence involved nearly all lymphocyte subsets, and 2 weeks of hydrogen treatment significantly improved most of these indexes. 20 The effects of hydrogen therapy on advanced NSCLC patients and middle-aged non-tumor participants in this study appear to be contradictory. The reason for this may be that the lymphocytes of patients with progressive tumors and those of non-tumor patients are quite different.…”

“… 16 Thus, we tested whether hydrogen gas inhalation can rescue the function of exhausted and senescent lymphocytes, as hydrogen gas was reported to protect the mitochondrial function of human lymphocytes. 17 18 19 By comparing the immune functions of advanced non-small cell lung cancer patients before and after hydrogen inhalation, we found that 2 weeks of hydrogen inhalation was enough to reverse multiple senescent or exhausted cell subsets into functional subsets, 20 so we used the same hydrogen inhalation duration during this study. There were no obvious changes in any T cell subsets due to hydrogen inhalation in either cell number, memory phenotype, differentiation phenotype or senescent or exhausted phenotype.…”

“…The number and function of immune cells of patients with advanced NSCLC are significantly lower than those of middle-aged participants, which becomes the basis for the high-flow hydrogen therapy to play a therapeutic role. 20 Therefore, it can be speculated that the high-flow hydrogen therapy is a regulatory therapy that can restore the damaged immune system to function, but has little effect on the normal immune system.…”

“…Prior to this study, we recruited 20 patients with advanced NSCLC, who underwent high-flow (not high concentration) hydrogen therapy for 2 weeks (4 hours per day, also 3 L/min, 66.7% hydrogen, 33.3% oxygen) before receiving standard treatments. 20 Before hydrogen inhalation, abnormally high indexes of the patients included exhausted Tc cells, senescent Tc cells, and killer Vδ1 cells. After 2 weeks of hydrogen therapy, the number of exhausted and senescent Tc cells decreased to within the normal range, and there was an increase in the number of killer Vδ 1 cells.…”

Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis

“…In addition, reports indicated that the antioxidant effect of H 2 was dose-dependent, and the concentration of H 2 in blood and tissues was dependent on the time and concentration of inhalation (Fukuda et al, 2007 ). In recent years, the administration of a mixture of H 2 and O 2 gases (66% H 2 ; 33% O 2 ), obtained by the electrolysis of water, for research and clinical investigation has become more and more common (Li H. et al, 2017 ; Chen et al, 2020 ). The application of high concentrations of H 2 gas may result in more effective outcomes.…”