Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status.
Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status.
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DOI：
10.1158/2326-6066.cir-18-0174
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发表时间：
2018-11
影响因子：
10.1
通讯作者：
Ogino S
中科院分区：
文献类型：
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作者：
Hamada T;Zhang X;Mima K;Bullman S;Sukawa Y;Nowak JA;Kosumi K;Masugi Y;Twombly TS;Cao Y;Song M;Liu L;da Silva A;Shi Y;Gu M;Li W;Koh H;Nosho K;Inamura K;Keum N;Wu K;Meyerhardt JA;Kostic AD;Huttenhower C;Garrett WS;Meyerson M;Giovannucci EL;Chan AT;Fuchs CS;Nishihara R;Giannakis M;Ogino S
结直肠癌组织中具核梭杆菌的存在与微卫星不稳定性 (MSI)、较低水平的 T 细胞浸润和不良的临床结果有关。考虑到具有高或低 MSI 的癌症的肿瘤免疫微环境的差异，我们假设具核梭菌与免疫反应的关联可能因肿瘤 MSI 状态而异。我们使用护士健康研究和健康专业人员随访研究中 1,041 名直肠癌和结肠癌患者的样本，通过定量聚合酶链反应测定法测量了肿瘤组织中的具核梭菌 DNA。使用多变量逻辑回归模型来检查具核梭杆菌状态与肿瘤 MSI 状态层中 CD3+ 细胞、CD8+ 细胞、CD45RO (PTPRC)+ 细胞或 FOXP3+ 细胞的组织病理学淋巴细胞反应或密度之间的关联。我们调整了潜在的混杂因素，包括 CpG 岛甲基化表型、LINE-1 甲基化以及 KRAS、BRAF 和 PIK3CA 突变。具核梭菌与肿瘤浸润淋巴细胞 (TIL) 和肿瘤内腺周反应的关联因肿瘤 MSI 状态而异 (Pinteraction = 0.002)。 F. nucleatum 的存在与 MSI 高肿瘤中的 TIL 呈负相关（多变量比值比，0.45；95% 置信区间，0.22–0.92），但与非 MSI 高肿瘤中的 TIL 呈正相关（多变量比值比，1.91；95% 置信区间，1.12–3.25）。瘤周淋巴细胞反应、克罗恩病样淋巴反应或 T 细胞密度没有观察到显着的差异相关性。总之，具核梭杆菌与结直肠癌免疫反应的关联因肿瘤 MSI 状态而异，表明具核梭杆菌和 MSI 状态相互作用，影响抗肿瘤免疫反应。
The presence of Fusobacterium nucleatum in colorectal carcinoma tissue has been associated with microsatellite instability (MSI), lower-level T-cell infiltrates, and poor clinical outcomes. Considering differences in the tumor-immune microenvironment of carcinomas with high or low MSI, we hypothesized that the association of F. nucleatum with immune response might differ by tumor MSI status. Using samples from 1,041 rectal and colon cancer patients within the Nurses’ Health Study and Health Professionals Follow-up Study, we measured F. nucleatum DNA in tumor tissue by a quantitative polymerase chain reaction assay. Multivariable logistic regression models were used to examine the association between F. nucleatum status and histopathologic lymphocytic reactions or density of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells in strata of tumor MSI status. We adjusted for potential confounders including CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. The association of F. nucleatum with tumor-infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed by tumor MSI status (Pinteraction = 0.002). The presence of F. nucleatum was negatively associated with TIL in MSI-high tumors (multivariable odds ratio, 0.45; 95% confidence interval, 0.22–0.92), but positively associated with TIL in non-MSI-high tumors (multivariable odds ratio, 1.91; 95% confidence interval, 1.12–3.25). No significant differential association was observed for peritumoral lymphocytic reaction, Crohn’s-like lymphoid reaction, or T-cell densities. In conclusion, the association of F. nucleatum with immune response to colorectal carcinoma differs by tumor MSI status, suggesting that F. nucleatum and MSI status interact to affect anti-tumor immune reactions.