低剂量酒精诱导的小鼠原位移植肿瘤抑制与t细胞反应相关

IF 3.5 4区 医学 Q3 CELL BIOLOGY Pathobiology Pub Date : 2023-01-01 DOI:10.1159/000524478
Akiko Kimoto, Shoma Kunisho, Ryohei Morita, Minako Onishi, Qian Zhou, Atsushi Ono, Daiki Miki, Fumio Shimamoto, Yasuhiko Kitadai
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引用次数: 0

摘要

引言:低剂量饮酒对结直肠癌发展的影响尚不清楚。流行病学研究报告说,少量饮酒的人的死亡率低于不饮酒者和酗酒者。这种现象被称为酒精的“j曲线效应”。本研究检测了低剂量酒精(0.5%、1%和2%)对移植结肠癌模型中肿瘤生长的影响。方法:采用BALB/c和BALB/c裸鼠进行t细胞免疫分析。将同源CT26小鼠结肠癌细胞植入盲肠壁上,并监测由此产生的t细胞免疫效应。结果:与对照组小鼠相比,低剂量(0.5%)酒精可明显抑制原位肿瘤的生长。相反,将同一细胞系的细胞注射到裸鼠盲肠壁上,未观察到肿瘤生长抑制。通过组织病理学和RNA序列分析来阐明肿瘤生长抑制的机制。肿瘤CD8+ T淋巴细胞升高,细胞因子水平改变。利用盲肠内容物的16S rRNA基因测序进行微生物组分析,发现在酒精组中,schaedlmucispirillum schaedleri和Clostridium cocleatum的丰度分别下降和增加。讨论/结论:摄入一定量的酒精会导致T淋巴细胞浸润,这可能会增强小鼠结直肠癌模型的免疫反应性。
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Low-Dose Alcohol-Induced Inhibition of Mouse Orthotopically Transplanted Tumors Is Associated with T-Cell Response.

Introduction: The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers and heavy drinkers. This phenomenon has been labeled the "J-curve effect" of alcohol. This study examined the effects of low-dose alcohol (0.5%, 1%, and 2%) on tumor growth in a transplant colon cancer model.

Methods: BALB/c and BALB/c nude mice were used to analyze T-cell immunity. Syngeneic CT26 murine colon cancer cells were implanted into the cecal wall, and the resulting T-cell immune effects were monitored.

Results: The growth of orthotopic tumors was markedly inhibited upon ingestion of low-dose (0.5%) alcohol compared with that in the control mice. In contrast, cells from the same line were injected into the cecal wall of nude mice, and tumor growth inhibition was not observed. Histopathological and RNA sequence analyses were performed to elucidate the mechanisms underlying tumor growth inhibition. An increase in tumor CD8+ T lymphocytes and changes in cytokine levels were observed. Microbiome analysis using 16S rRNA gene sequencing of cecal contents was performed and revealed Mucispirillum schaedleri and Clostridium cocleatum showed decreased and increased abundance, respectively, in the alcohol group.

Discussion/conclusion: Ingesting a threshold amount of alcohol results in the infiltration of T lymphocytes, which may enhance immune responsiveness in mouse colorectal cancer models.

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来源期刊
Pathobiology
Pathobiology 医学-病理学
CiteScore
8.50
自引率
0.00%
发文量
47
审稿时长
>12 weeks
期刊介绍: ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.
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