Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment
cGAS and AIM2 are CDSs that are activated in the presence of cytosolic dsDNA and are expressed in various cell types, including immune and tumor cells. The recognition of tumor-derived dsDNA by CDSs in the cytosol of tumor-infiltrating dendritic cells (TIDCs) activates the innate and acquired immuni...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/7/2114 |
| _version_ | 1797608268729679872 |
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| author | Keitaro Fukuda |
| author_facet | Keitaro Fukuda |
| author_sort | Keitaro Fukuda |
| collection | DOAJ |
| description | cGAS and AIM2 are CDSs that are activated in the presence of cytosolic dsDNA and are expressed in various cell types, including immune and tumor cells. The recognition of tumor-derived dsDNA by CDSs in the cytosol of tumor-infiltrating dendritic cells (TIDCs) activates the innate and acquired immunity, thereby enhancing anti-tumor immune responses. STING is the downstream signaling effector of cGAS that induces type I interferon (IFN) signaling. Owing to their ability to activate TIDCs, STING agonists have been intratumorally injected in several clinical trials to enhance the anti-tumor immune response elicited by immune checkpoint antibodies. However, they have shown minimal effect, suggesting the importance of optimizing the dose and route of administration for STING agonists and deciphering other immune pathways that contribute to anti-tumor immune responses. Recent studies have revealed that AIM2 activity induces pro-tumor growth through multiple parallel pathways, including inhibition of STING-type I IFN signaling. Thus, AIM2 could be a potential molecular target for cancer immunotherapies. This review summarizes the current research on the roles of cGAS, STING, and AIM2 in immune cells and tumor cells in the tumor microenvironment and discusses the future prospects of anti-tumor treatment approaches based on these molecules. |
| first_indexed | 2024-03-11T05:41:14Z |
| format | Article |
| id | doaj.art-ba94a37e13a34149891539b1fe69e101 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:41:14Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ba94a37e13a34149891539b1fe69e1012023-11-17T16:26:22ZengMDPI AGCancers2072-66942023-04-01157211410.3390/cancers15072114Immune Regulation by Cytosolic DNA Sensors in the Tumor MicroenvironmentKeitaro Fukuda0RIKEN Center for Integrative Medical Sciences (IMS), Laboratory for Skin Homeostasis, Yokohama 230-0045, JapancGAS and AIM2 are CDSs that are activated in the presence of cytosolic dsDNA and are expressed in various cell types, including immune and tumor cells. The recognition of tumor-derived dsDNA by CDSs in the cytosol of tumor-infiltrating dendritic cells (TIDCs) activates the innate and acquired immunity, thereby enhancing anti-tumor immune responses. STING is the downstream signaling effector of cGAS that induces type I interferon (IFN) signaling. Owing to their ability to activate TIDCs, STING agonists have been intratumorally injected in several clinical trials to enhance the anti-tumor immune response elicited by immune checkpoint antibodies. However, they have shown minimal effect, suggesting the importance of optimizing the dose and route of administration for STING agonists and deciphering other immune pathways that contribute to anti-tumor immune responses. Recent studies have revealed that AIM2 activity induces pro-tumor growth through multiple parallel pathways, including inhibition of STING-type I IFN signaling. Thus, AIM2 could be a potential molecular target for cancer immunotherapies. This review summarizes the current research on the roles of cGAS, STING, and AIM2 in immune cells and tumor cells in the tumor microenvironment and discusses the future prospects of anti-tumor treatment approaches based on these molecules.https://www.mdpi.com/2072-6694/15/7/2114cytosolic DNA sensorcGASSTINGtype I IFNAIM2IL-1β |
| spellingShingle | Keitaro Fukuda Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment Cancers cytosolic DNA sensor cGAS STING type I IFN AIM2 IL-1β |
| title | Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment |
| title_full | Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment |
| title_fullStr | Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment |
| title_full_unstemmed | Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment |
| title_short | Immune Regulation by Cytosolic DNA Sensors in the Tumor Microenvironment |
| title_sort | immune regulation by cytosolic dna sensors in the tumor microenvironment |
| topic | cytosolic DNA sensor cGAS STING type I IFN AIM2 IL-1β |
| url | https://www.mdpi.com/2072-6694/15/7/2114 |
| work_keys_str_mv | AT keitarofukuda immuneregulationbycytosolicdnasensorsinthetumormicroenvironment |