| Title: | Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer |
| Journal: | Nature Communications |
| Published: | 1 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40595642/ |
| DOI: | https://doi.org/10.1038/s41467-025-60958-0 |
| URL: | https://www.nature.com/articles/s41467-025-60958-0.pdf |
Publication 16383
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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.</p>
16 Keywords
- Animals
- CD8-Positive T-Lymphocytes
- Caffeine
- Cell Line, Tumor
- Colorectal Neoplasms
- Female
- Humans
- Immunotherapy
- Indoleamine-Pyrrole 2,3,-Dioxygenase
- Kynurenine
- Male
- Mice
- Mice, Inbred C57BL
- Programmed Cell Death 1 Receptor
- Signal Transduction
- Xenograft Model Antitumor Assays
10 Authors
- Yuechen Liu
- Zhengyu Liu
- Yating Hu
- Yunyan Ling
- Shunjie Qing
- Yang Liu
- Yizhi Zhan
- Zhiyong Shen
- Yuan Fang
- Haijun Deng
1 Application
| Application ID | Title |
|---|---|
| 92668 | Development and validation of enhanced prediction models based on polygenic analysis and clinical factors for chronic diseases |
Enabling scientific discoveries that improve human health