Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.
Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.
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DOI：
10.1001/jamaoncol.2015.1377
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发表时间：
2015-08
期刊：
影响因子：
28.4
通讯作者：
Ogino S
中科院分区：
文献类型：
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作者：
Mima K;Sukawa Y;Nishihara R;Qian ZR;Yamauchi M;Inamura K;Kim SA;Masuda A;Nowak JA;Nosho K;Kostic AD;Giannakis M;Watanabe H;Bullman S;Milner DA;Harris CC;Giovannucci E;Garraway LA;Freeman GJ;Dranoff G;Chan AT;Garrett WS;Huttenhower C;Fuchs CS;Ogino S
有证据表明肠道微生物组、免疫和肠道肿瘤发生之间存在复杂的联系。为了针对结直肠癌的预防和治疗的微生物群和免疫，需要更好地了解肿瘤微环境中微生物和免疫细胞之间的关系。实验证据表明，具核梭杆菌可能通过下调抗肿瘤 T 细胞介导的适应性免疫来促进结肠肿瘤的发展。检验结直肠癌组织中较高数量的具核梭杆菌与肿瘤组织中较低密度的 T 细胞相关的假设。对美国两项全国性前瞻性队列研究中的结直肠癌病例进行了横断面分析。采用定量聚合酶链反应法测定结直肠癌组织中具核梭杆菌的含量；我们同样将阳性病例分为两类（高与低）。采用多变量序数逻辑回归分析来评估具核梭杆菌数量与肿瘤组织中 T 细胞密度（四分位数）的关联，控制临床和肿瘤分子特征，包括微卫星不稳定性、CpG 岛甲基化表型、LINE-1 甲基化以及 KRAS、BRAF 和 PIK3CA 突变状态。我们将两侧 α 水平调整为 0.013 以进行多重假设检验。护士健康研究和卫生专业人员后续研究。结肠癌和直肠癌598例。通过组织微阵列免疫组织化学和计算机辅助图像分析测定肿瘤组织中 CD3+、CD8+、CD45RO (PTPRC)+ 和 FOXP3+ T 细胞的密度。 598 例结直肠癌组织中检出具核梭杆菌，76 例（13%）。与具核梭杆菌阴性病例相比，具核梭杆菌高病例与 CD3+ T 细胞密度呈负相关（CD3+ T 细胞四分位数类别增加一个单位作为结果：多变量比值比，0.47；95% 置信区间，0.26 至 0.87；Ptrend = 0.006）。具核梭杆菌的数量与 CD8+、CD45RO+ 或 FOXP3+ T 细胞的密度没有显着相关性 (Ptrend > 0.013)。组织中具核梭杆菌的数量与结直肠癌组织中的 CD3+ T 细胞密度呈负相关。经过验证，我们的人群数据可能会为进一步研究梭杆菌和宿主免疫在致癌过程中的潜在相互作用作用提供动力。
Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by down-regulating antitumor T-cell-mediated adaptive immunity. To test the hypothesis that higher amount of Fusobacterium nucleatum in colorectal carcinoma tissue is associated with lower density of T-cells in tumor tissue. A cross-sectional analysis was conducted on colorectal carcinoma cases in two U.S. nationwide prospective cohort studies. The amount of Fusobacterium nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high versus low). Multivariable ordinal logistic regression analysis was conducted to assess associations of the amount of Fusobacterium nucleatum with densities (quartiles) of T-cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted two-sided α level to 0.013 for multiple hypothesis testing. The Nurses’ Health Study and the Health Professionals Follow-up Study. 598 colon and rectal carcinoma cases. Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ T-cells in tumor tissue, determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Fusobacterium nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with Fusobacterium nucleatum-negative cases, Fusobacterium nucleatum-high cases were inversely associated with the density of CD3+ T-cells (for a unit increase in quartile categories of CD3+ T-cells as an outcome: multivariable odds ratio, 0.47; 95% confidence interval, 0.26 to 0.87; Ptrend = 0.006). The amount of Fusobacterium nucleatum was not significantly associated with the density of CD8+, CD45RO+, or FOXP3+ T-cells (Ptrend > 0.013). The amount of tissue Fusobacterium nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. Upon validation, our human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in carcinogenesis.