Exploiting RIG-I-like receptor pathway for cancer immunotherapy
Abstract RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-023-01405-9 |
| _version_ | 1811165777713168384 |
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| author | Yangfu Jiang Hongying Zhang Jiao Wang Jinzhu Chen Zeyu Guo Yongliang Liu Hui Hua |
| author_facet | Yangfu Jiang Hongying Zhang Jiao Wang Jinzhu Chen Zeyu Guo Yongliang Liu Hui Hua |
| author_sort | Yangfu Jiang |
| collection | DOAJ |
| description | Abstract RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy. |
| first_indexed | 2024-04-10T15:42:06Z |
| format | Article |
| id | doaj.art-769a9a401f624fdb98ed64676b21be13 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-10T15:42:06Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-769a9a401f624fdb98ed64676b21be132023-02-12T12:20:07ZengBMCJournal of Hematology & Oncology1756-87222023-02-0116112710.1186/s13045-023-01405-9Exploiting RIG-I-like receptor pathway for cancer immunotherapyYangfu Jiang0Hongying Zhang1Jiao Wang2Jinzhu Chen3Zeyu Guo4Yongliang Liu5Hui Hua6Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityLaboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversitySchool of Basic Medicine, Chengdu University of Traditional Chinese MedicineLaboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityLaboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityLaboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityLaboratory of Stem Cell Biology, West China Hospital, Sichuan UniversityAbstract RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.https://doi.org/10.1186/s13045-023-01405-9CancerImmunotherapyOncolytic virusRIG-IRIG-I-like receptorsRNA therapy |
| spellingShingle | Yangfu Jiang Hongying Zhang Jiao Wang Jinzhu Chen Zeyu Guo Yongliang Liu Hui Hua Exploiting RIG-I-like receptor pathway for cancer immunotherapy Journal of Hematology & Oncology Cancer Immunotherapy Oncolytic virus RIG-I RIG-I-like receptors RNA therapy |
| title | Exploiting RIG-I-like receptor pathway for cancer immunotherapy |
| title_full | Exploiting RIG-I-like receptor pathway for cancer immunotherapy |
| title_fullStr | Exploiting RIG-I-like receptor pathway for cancer immunotherapy |
| title_full_unstemmed | Exploiting RIG-I-like receptor pathway for cancer immunotherapy |
| title_short | Exploiting RIG-I-like receptor pathway for cancer immunotherapy |
| title_sort | exploiting rig i like receptor pathway for cancer immunotherapy |
| topic | Cancer Immunotherapy Oncolytic virus RIG-I RIG-I-like receptors RNA therapy |
| url | https://doi.org/10.1186/s13045-023-01405-9 |
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