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具核梭杆菌与结直肠癌肝转移抗肿瘤免疫的关系。

Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis.

机构信息

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.

出版信息

Cancer Sci. 2021 Nov;112(11):4470-4477. doi: 10.1111/cas.15126. Epub 2021 Sep 23.

Abstract

Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8 T cells, CD33 cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163 cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8 T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8 T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.

摘要

具核梭杆菌存在于 8%-13%的人类结直肠癌中,并在动物模型中显示出抑制原发性结直肠肿瘤免疫反应的作用。因此,我们假设具核梭杆菌的存在可能与结直肠癌肝转移(CRLM)中 T 细胞密度降低有关。我们使用定量 PCR 检测了 181 个 CRLM 标本中的具核梭杆菌 DNA。通过免疫组织化学染色确定了 CRLM 组织中 CD8 T 细胞、CD33 细胞(髓系来源抑制细胞 [MDSCs]的标志物)和 CD163 细胞(肿瘤相关巨噬细胞 [TAMs]的标志物)的密度。在 181 个 CRLM 标本中检测到 8 个(4.4%)具核梭杆菌。与具核梭杆菌阴性的 CRLM 相比,具核梭杆菌阳性的 CRLM 中 CD8 T 细胞的密度明显更低(P =.033),MDSC 的密度更高(P =.001)。具核梭杆菌与 TAMs 密度之间的关联无统计学意义(P =.70)。具核梭杆菌的存在与 CRLM 组织中 CD8 T 细胞密度降低和 MDSC 密度升高有关。经验证,我们的发现可能为开发涉及靶向微生物群和免疫细胞以预防和治疗 CRLM 的策略提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c46/8586672/ab96a9872780/CAS-112-4470-g004.jpg

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