S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer
Abstract Metabolite nutrients within the tumor microenvironment shape both tumor progression and immune cell functionality. It remains elusive how the metabolic interaction between T cells and tumor cells results in different anti-cancer immunotherapeutic responses. Here, we use untargeted metabolom...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Cancer & Metabolism |
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| Online Access: | https://doi.org/10.1186/s40170-025-00394-2 |
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| author | Xiaohua Yang Tianzhang Kou Hongmiao Wang Ji Zhu Zheng-Jiang Zhu Yuping Cai |
| author_facet | Xiaohua Yang Tianzhang Kou Hongmiao Wang Ji Zhu Zheng-Jiang Zhu Yuping Cai |
| author_sort | Xiaohua Yang |
| collection | DOAJ |
| description | Abstract Metabolite nutrients within the tumor microenvironment shape both tumor progression and immune cell functionality. It remains elusive how the metabolic interaction between T cells and tumor cells results in different anti-cancer immunotherapeutic responses. Here, we use untargeted metabolomics to investigate the metabolic heterogeneity in patients with colorectal cancer (CRC). Our analysis reveals enhanced S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) metabolism in microsatellite stable (MSS) CRC, a subtype known for its resistance to immunotherapy. Functional studies reveal that SAM and SAH enhance the initial activation and effector functions of CD8+ T cells. Instead, cancer cells outcompete CD8+ T cells for SAM and SAH availability to impair T cell survival. In vivo, SAM supplementation promotes T cell proliferation and reduces exhaustion of the tumor-infiltrating CD8+ T cells, thus suppressing tumor growth in tumor-bearing mice. This study uncovers the metabolic crosstalk between T cells and tumor cells, which drives the development of tumors resistant to immunotherapy. |
| format | Article |
| id | doaj-art-eaa9b0f2ff114ebca8ea3313bc5eb72a |
| institution | DOAJ |
| issn | 2049-3002 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer & Metabolism |
| spelling | doaj-art-eaa9b0f2ff114ebca8ea3313bc5eb72a2025-08-20T03:08:44ZengBMCCancer & Metabolism2049-30022025-05-0113111510.1186/s40170-025-00394-2S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancerXiaohua Yang0Tianzhang Kou1Hongmiao Wang2Ji Zhu3Zheng-Jiang Zhu4Yuping Cai5Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesDepartment of Radiation Oncology, Zhejiang Cancer HospitalInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of SciencesAbstract Metabolite nutrients within the tumor microenvironment shape both tumor progression and immune cell functionality. It remains elusive how the metabolic interaction between T cells and tumor cells results in different anti-cancer immunotherapeutic responses. Here, we use untargeted metabolomics to investigate the metabolic heterogeneity in patients with colorectal cancer (CRC). Our analysis reveals enhanced S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) metabolism in microsatellite stable (MSS) CRC, a subtype known for its resistance to immunotherapy. Functional studies reveal that SAM and SAH enhance the initial activation and effector functions of CD8+ T cells. Instead, cancer cells outcompete CD8+ T cells for SAM and SAH availability to impair T cell survival. In vivo, SAM supplementation promotes T cell proliferation and reduces exhaustion of the tumor-infiltrating CD8+ T cells, thus suppressing tumor growth in tumor-bearing mice. This study uncovers the metabolic crosstalk between T cells and tumor cells, which drives the development of tumors resistant to immunotherapy.https://doi.org/10.1186/s40170-025-00394-2Metabolite nutrientsCD8+ T cell functionMicrosatellite stable colorectal cancerMetabolomicsS-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) metabolism |
| spellingShingle | Xiaohua Yang Tianzhang Kou Hongmiao Wang Ji Zhu Zheng-Jiang Zhu Yuping Cai S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer Cancer & Metabolism Metabolite nutrients CD8+ T cell function Microsatellite stable colorectal cancer Metabolomics S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) metabolism |
| title | S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer |
| title_full | S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer |
| title_fullStr | S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer |
| title_full_unstemmed | S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer |
| title_short | S-adenosylmethionine metabolism shapes CD8+ T cell functions in colorectal cancer |
| title_sort | s adenosylmethionine metabolism shapes cd8 t cell functions in colorectal cancer |
| topic | Metabolite nutrients CD8+ T cell function Microsatellite stable colorectal cancer Metabolomics S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) metabolism |
| url | https://doi.org/10.1186/s40170-025-00394-2 |
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