Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity
Abstract Tumor immunotherapy offers a new paradigm to treat cancer; however, the existing regimens are accompanied by the dilemma of insufficient therapeutic outcomes and off‐target adverse effects. The intestinal immune system contains a bulk of immune cells, which can be important contributors to...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202302910 |
| _version_ | 1797389533237477376 |
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| author | Xinran Cao Yuan Xu Chen Zhou Jiawei Huo Shenge Su Lei Liu Ziran Zhu Lei Li Wang Jia Chunru Wang Mingming Zhen |
| author_facet | Xinran Cao Yuan Xu Chen Zhou Jiawei Huo Shenge Su Lei Liu Ziran Zhu Lei Li Wang Jia Chunru Wang Mingming Zhen |
| author_sort | Xinran Cao |
| collection | DOAJ |
| description | Abstract Tumor immunotherapy offers a new paradigm to treat cancer; however, the existing regimens are accompanied by the dilemma of insufficient therapeutic outcomes and off‐target adverse effects. The intestinal immune system contains a bulk of immune cells, which can be important contributors to the maintenance of systemic immune homeostasis. However, manipulating intestinal immunity to achieve systemic anti‐tumor immunity is extremely challenging. Here, an oral immunotherapy strategy is reported using immune‐enhancing fullerenes (IEF) that can reinvigorate anti‐tumor immunity via immune cell‐metabolic reprogramming of intestinal immune cells. Findings show that IEF can remodel anti‐inflammatory macrophages into tumor‐killing macrophages by regulating the energy metabolism pathway from oxidative phosphorylation (OXPHOS) to glycolysis. Consequently, IEF can reprogram the immunosuppressive intestinal immunity and enhance sys temic immunity in vivo, thereby boosting anti‐tumor immunity and converting “cold” tumors into “hot” tumors. Oral immunotherapy strategy, modulating autoimmune cells in the intestine and achieving systemic anti‐tumor immunity, can ensure safe and efficient tumor immunotherapy. |
| first_indexed | 2024-03-08T22:58:22Z |
| format | Article |
| id | doaj.art-47cb58f1793d4656b4d32da9b82c2d38 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T22:58:22Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-47cb58f1793d4656b4d32da9b82c2d382023-12-16T04:16:14ZengWileyAdvanced Science2198-38442023-12-011035n/an/a10.1002/advs.202302910Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor ImmunityXinran Cao0Yuan Xu1Chen Zhou2Jiawei Huo3Shenge Su4Lei Liu5Ziran Zhu6Lei Li7Wang Jia8Chunru Wang9Mingming Zhen10Beijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaUniversity of Chinese Academy of Sciences Beijing 100049 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaBeijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of Sciences Beijing 100190 ChinaAbstract Tumor immunotherapy offers a new paradigm to treat cancer; however, the existing regimens are accompanied by the dilemma of insufficient therapeutic outcomes and off‐target adverse effects. The intestinal immune system contains a bulk of immune cells, which can be important contributors to the maintenance of systemic immune homeostasis. However, manipulating intestinal immunity to achieve systemic anti‐tumor immunity is extremely challenging. Here, an oral immunotherapy strategy is reported using immune‐enhancing fullerenes (IEF) that can reinvigorate anti‐tumor immunity via immune cell‐metabolic reprogramming of intestinal immune cells. Findings show that IEF can remodel anti‐inflammatory macrophages into tumor‐killing macrophages by regulating the energy metabolism pathway from oxidative phosphorylation (OXPHOS) to glycolysis. Consequently, IEF can reprogram the immunosuppressive intestinal immunity and enhance sys temic immunity in vivo, thereby boosting anti‐tumor immunity and converting “cold” tumors into “hot” tumors. Oral immunotherapy strategy, modulating autoimmune cells in the intestine and achieving systemic anti‐tumor immunity, can ensure safe and efficient tumor immunotherapy.https://doi.org/10.1002/advs.202302910cellular metabolismimmune‐enhancing fullerenesintestinal immunosuppressionproteomicstumor immunotherapy |
| spellingShingle | Xinran Cao Yuan Xu Chen Zhou Jiawei Huo Shenge Su Lei Liu Ziran Zhu Lei Li Wang Jia Chunru Wang Mingming Zhen Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity Advanced Science cellular metabolism immune‐enhancing fullerenes intestinal immunosuppression proteomics tumor immunotherapy |
| title | Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity |
| title_full | Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity |
| title_fullStr | Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity |
| title_full_unstemmed | Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity |
| title_short | Oral Immunotherapy Reshapes Intestinal Immunosuppression via Metabolic Reprogramming to Enhance Systemic Anti‐Tumor Immunity |
| title_sort | oral immunotherapy reshapes intestinal immunosuppression via metabolic reprogramming to enhance systemic anti tumor immunity |
| topic | cellular metabolism immune‐enhancing fullerenes intestinal immunosuppression proteomics tumor immunotherapy |
| url | https://doi.org/10.1002/advs.202302910 |
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