The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/10/2826 |
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| author | Shotaro Nakajima Akinao Kaneta Hirokazu Okayama Katsuharu Saito Tomohiro Kikuchi Eisei Endo Takuro Matsumoto Satoshi Fukai Mei Sakuma Takahiro Sato Kosaku Mimura Motonobu Saito Zenichiro Saze Wataru Sakamoto Hisashi Onozawa Tomoyuki Momma Koji Kono |
| author_facet | Shotaro Nakajima Akinao Kaneta Hirokazu Okayama Katsuharu Saito Tomohiro Kikuchi Eisei Endo Takuro Matsumoto Satoshi Fukai Mei Sakuma Takahiro Sato Kosaku Mimura Motonobu Saito Zenichiro Saze Wataru Sakamoto Hisashi Onozawa Tomoyuki Momma Koji Kono |
| author_sort | Shotaro Nakajima |
| collection | DOAJ |
| description | The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8<sup>+</sup> T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS<sup>−</sup>/STING<sup>−</sup>) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS<sup>+</sup>/STING<sup>+</sup>) in tumor cells. The frequency of cGAS<sup>+</sup>/STING<sup>+</sup> cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8<sup>+</sup> and/or CD4<sup>+</sup> T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC. |
| first_indexed | 2024-03-11T03:51:59Z |
| format | Article |
| id | doaj.art-b3d0f9ed694246278629a1a94cffaf92 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:51:59Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b3d0f9ed694246278629a1a94cffaf922023-11-18T00:49:31ZengMDPI AGCancers2072-66942023-05-011510282610.3390/cancers15102826The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal CancerShotaro Nakajima0Akinao Kaneta1Hirokazu Okayama2Katsuharu Saito3Tomohiro Kikuchi4Eisei Endo5Takuro Matsumoto6Satoshi Fukai7Mei Sakuma8Takahiro Sato9Kosaku Mimura10Motonobu Saito11Zenichiro Saze12Wataru Sakamoto13Hisashi Onozawa14Tomoyuki Momma15Koji Kono16Department of Multidisciplinary Treatment of Cancer and Regional Medical Support, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Multidisciplinary Treatment of Cancer and Regional Medical Support, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanThe cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8<sup>+</sup> T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS<sup>−</sup>/STING<sup>−</sup>) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS<sup>+</sup>/STING<sup>+</sup>) in tumor cells. The frequency of cGAS<sup>+</sup>/STING<sup>+</sup> cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8<sup>+</sup> and/or CD4<sup>+</sup> T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC.https://www.mdpi.com/2072-6694/15/10/2826colorectal cancer (CRC)pMMR/MSS CRCtumor cell-intrinsic cGAS-STINGCD8<sup>+</sup>,CD4<sup>+</sup> T cells |
| spellingShingle | Shotaro Nakajima Akinao Kaneta Hirokazu Okayama Katsuharu Saito Tomohiro Kikuchi Eisei Endo Takuro Matsumoto Satoshi Fukai Mei Sakuma Takahiro Sato Kosaku Mimura Motonobu Saito Zenichiro Saze Wataru Sakamoto Hisashi Onozawa Tomoyuki Momma Koji Kono The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer Cancers colorectal cancer (CRC) pMMR/MSS CRC tumor cell-intrinsic cGAS-STING CD8<sup>+</sup>,CD4<sup>+</sup> T cells |
| title | The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer |
| title_full | The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer |
| title_fullStr | The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer |
| title_full_unstemmed | The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer |
| title_short | The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8<sup>+</sup> T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer |
| title_sort | impact of tumor cell intrinsic expression of cyclic gmp amp synthase cgas stimulator of interferon genes sting on the infiltration of cd8 sup sup t cells and clinical outcomes in mismatch repair proficient microsatellite stable colorectal cancer |
| topic | colorectal cancer (CRC) pMMR/MSS CRC tumor cell-intrinsic cGAS-STING CD8<sup>+</sup>,CD4<sup>+</sup> T cells |
| url | https://www.mdpi.com/2072-6694/15/10/2826 |
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