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journal article·2024-07Open access

Hydrogen Therapy Reverses Cancer‐Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti‐Tumor Immunity

Xiaoyan Meng, Zhonglong Liu, Liang Deng, Yangzi Yang, Yingchun Zhu, Xiaoying Sun, Yongqiang Hao, Yue He, Jingke Fu

Advanced Science· Volume 11· Issue 28
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Abstract

Abstract Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer‐associated fibroblasts (CAFs) show multiple tumor‐promoting effects and can induce tumor immune evasion and drug‐resistance. Regulating CAFs can be a potential strategy to augment systemic anti‐tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs’ tumor‐promoting and immune‐suppressive phenotypes. Accordingly, a controllable and TME‐responsive hydrogen therapy based on a CaCO3 nanoparticles‐coated magnesium system (Mg‐CaCO3) is developed. The hydrogen therapy by Mg‐CaCO3 can not only directly kill tumor cells, but also inhibit pro‐tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg‐CaCO3 can significantly suppress tumor growth, turn the “cold” primary tumor into “hot”, and stimulate systematic anti‐tumor immunity, which is confirmed by the bilateral tumor transplantation models of “cold tumor” (4T1 cells) and “hot tumor” (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti‐tumor immune stimulating strategy by remodeling tumor stromal microenvironment.
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Research context

NanomaterialsBiomaterials

OpenAlex topics: Hydrogen's biological and therapeutic effects · Chemical Reactions and Isotopes · Medical and Biological Ozone Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oral Maxillofacial & Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 P. R. China

College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Jiao Tong University Shanghai 200011 P. R. China

Shanghai Key Laboratory of Orthopaedic Implant Department of Orthopaedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 P. R. China

Clinical and Translational Research Center for 3D Printing Technology Shanghai Engineering Research Center of Innovative Orthopaedic Instruments and Personalized Medicine Shanghai 200011 P. R. China

Department of Orthopedic Surgery Spine Center Changzheng Hospital Navy Medical University No. 415 Fengyang Road Shanghai 200003 P. R. China

Key Laboratory of Inorganic Coating Materials Shanghai Institute of Ceramics Chinese Academy of Sciences Shanghai 200050 P. R. China

College of Sciences Shanghai University Shanghai 200444 P. R. China

Funding

National Natural Science Foundation of China · Shanghai Municipal Health Commission

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