Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer
Abstract Colorectal cancer (CRC) is a leading global health issue, ranking third in incidence and second in cancer mortality. Immunotherapy, effective mainly in mismatch repair-deficient CRC, may benefit from dietary interventions. This study investigates caffeine’s potential to boost programmed dea...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60958-0 |
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| _version_ | 1849402060359860224 |
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| author | Yuechen Liu Zhengyu Liu Yating Hu Yunyan Ling Shunjie Qing Yang Liu Yizhi Zhan Zhiyong Shen Yuan Fang Haijun Deng |
| author_facet | Yuechen Liu Zhengyu Liu Yating Hu Yunyan Ling Shunjie Qing Yang Liu Yizhi Zhan Zhiyong Shen Yuan Fang Haijun Deng |
| author_sort | Yuechen Liu |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is a leading global health issue, ranking third in incidence and second in cancer mortality. Immunotherapy, effective mainly in mismatch repair-deficient CRC, may benefit from dietary interventions. This study investigates caffeine’s potential to boost programmed death-1 (PD-1) immunotherapy efficacy in CRC, revealing that caffeine significantly reduces tumor growth, extends survival, and enhances CD8+ T cell activity in CRC by suppressing kynurenine pathway. Mechanistically, caffeine decreases kynurenine via the Krüppel-like factor 4 (KLF4)- Collagen type XII alpha 1 (COL12A1)- Mitogen-Activated Protein Kinase (MAPK)-Indoleamine 2,3-dioxygenase 1 (IDO1) axis, mitigating CD8+ T cell exhaustion. Combining caffeine with PD-1 therapy further prolongs survival, highlighting the value of integrating nutritional strategies into cancer treatment to improve outcomes and broaden therapeutic options. Here, we show caffeine can enhance PD-1 immunotherapy in CRC by suppressing kynurenine pathway, suggesting its potential as an adjunctive dietary therapy. |
| format | Article |
| id | doaj-art-484170ac28d24c128fa7ab5e62a9e46a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-484170ac28d24c128fa7ab5e62a9e46a2025-08-20T03:37:38ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-60958-0Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancerYuechen Liu0Zhengyu Liu1Yating Hu2Yunyan Ling3Shunjie Qing4Yang Liu5Yizhi Zhan6Zhiyong Shen7Yuan Fang8Haijun Deng9Department of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Pathology, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Colorectal cancer (CRC) is a leading global health issue, ranking third in incidence and second in cancer mortality. Immunotherapy, effective mainly in mismatch repair-deficient CRC, may benefit from dietary interventions. This study investigates caffeine’s potential to boost programmed death-1 (PD-1) immunotherapy efficacy in CRC, revealing that caffeine significantly reduces tumor growth, extends survival, and enhances CD8+ T cell activity in CRC by suppressing kynurenine pathway. Mechanistically, caffeine decreases kynurenine via the Krüppel-like factor 4 (KLF4)- Collagen type XII alpha 1 (COL12A1)- Mitogen-Activated Protein Kinase (MAPK)-Indoleamine 2,3-dioxygenase 1 (IDO1) axis, mitigating CD8+ T cell exhaustion. Combining caffeine with PD-1 therapy further prolongs survival, highlighting the value of integrating nutritional strategies into cancer treatment to improve outcomes and broaden therapeutic options. Here, we show caffeine can enhance PD-1 immunotherapy in CRC by suppressing kynurenine pathway, suggesting its potential as an adjunctive dietary therapy.https://doi.org/10.1038/s41467-025-60958-0 |
| spellingShingle | Yuechen Liu Zhengyu Liu Yating Hu Yunyan Ling Shunjie Qing Yang Liu Yizhi Zhan Zhiyong Shen Yuan Fang Haijun Deng Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer Nature Communications |
| title | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| title_full | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| title_fullStr | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| title_full_unstemmed | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| title_short | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| title_sort | caffeine enhances antitumor t cell activity by suppressing kynurenine pathway in colorectal cancer |
| url | https://doi.org/10.1038/s41467-025-60958-0 |
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