Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer.

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-07-01 DOI:10.1038/s41467-025-60958-0

Yuechen Liu, Zhengyu Liu, Yating Hu, Yunyan Ling, Shunjie Qing, Yang Liu, Yizhi Zhan, Zhiyong Shen, Yuan Fang, Haijun Deng

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引用次数: 0

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.

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咖啡因通过抑制犬尿氨酸途径增强结直肠癌抗肿瘤t细胞活性。

结直肠癌（CRC）是一个主要的全球健康问题，发病率排名第三，癌症死亡率排名第二。免疫疗法主要对错配修复缺陷的结直肠癌有效，可从饮食干预中获益。本研究探讨了咖啡因在CRC中提高程序性死亡-1 （PD-1）免疫治疗疗效的潜力，揭示了咖啡因通过抑制犬尿氨酸途径显著降低CRC肿瘤生长，延长生存期，提高CD8+ T细胞活性。在机制上，咖啡因通过kr pel样因子4 (KLF4)-胶原型XII α 1 (COL12A1)-丝裂原活化蛋白激酶(MAPK)-吲哚胺2,3-双加氧酶1 （IDO1）轴降低犬尿氨酸，减轻CD8+ T细胞衰竭。将咖啡因与PD-1治疗相结合进一步延长了生存期，强调了将营养策略整合到癌症治疗中以改善结果和拓宽治疗选择的价值。在这里，我们发现咖啡因可以通过抑制犬尿氨酸途径增强CRC的PD-1免疫治疗，这表明它有可能作为一种辅助饮食治疗。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.