DataVXAdvanced Functional MaterialsPaper
journal article·2025-09Open access

Reengineering the Tumor Oxygen Microenvironment in Radiotherapy to Enhance T‐Cell Function for Radio‐Immunotherapy

Zetong Chen, Qing He, Rui Qian, Jinzhou Cai, Ziqi Wang, Xuyi Zhou, Xinyang Zhang, Qiyun Wang, Hongwei Si, Jie Li, Kai Yang, Pei Pei

Advanced Functional Materials· Volume 35· Issue 38
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Source abstract

Abstract

Abstract Analyzing the relationship between tumor O 2 microenvironment (TOME) and immune microenvironment during radiotherapy and regulating it will provide new insights into the combination of radiotherapy and immunotherapy. In the experiments, it is observed that the exacerbation of tumor hypoxia after radiotherapy activated the HIF pathway, which, in turn, led to T‐cell exhaustion by upregulating PD‐L1 expression in the tumor and promoting the infiltration of MDSCs. To address this, a manganese ion‐doped Au–Pt nanozyme‐coated O 2 modulator (Mn‐Nz‐M) is designed and prepared to reengineer the TOME. First, the high catalase activity of Mn‐Nz‐M efficiently generated O 2 at the tumor‐site, modulating the TOME and improving radiotherapy efficacy. More importantly, studies in vitro and in vivo showed that Mn‐Nz‐M‐mediated improvement of TOME can reverse PD‐1 + T cell exhaustion post radiotherapy and activate T cell function. Additionally, the Mn 2+ released from Mn‐Nz‐M can simultaneously amplify the cGAS‐STING pathway to activate NK cells for anti‐tumor activity. This reengineering strategy of the TOME for radio‐immunotherapy not only eliminates primary solid tumors but also inhibits tumor metastasis, providing new insights and potential therapeutic targets for enhancing the interaction between radiotherapy and immunotherapy.
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Research context

Nanomaterials

OpenAlex topics: Cancer Immunotherapy and Biomarkers · Immunotherapy and Immune Responses · Nanoplatforms for cancer theranostics

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

Affiliations

Department of Nuclear Medicine The First Affiliated Hospital of Anhui Medical University Hefei Anhui Province 230022 P. R. China

Teaching and Research Section of Nuclear Medicine School of Basic Medical Sciences Anhui Medical University 81 Meishan Road Hefei Anhui 230032 P. R. China

Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor Nanfang Hospital The First School of Clinical Medicine Southern Medical University Guangzhou Guangzhou 510000 P. R. China

State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD‐X) Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University Suzhou Jiangsu 215123 P. R. China

Jiangsu Province Key laboratory in Anesthesiology School of Anesthesiology Xuzhou Medical University Xuzhou Jiangsu 221004 P. R. China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Anhui Province

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