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具核梭杆菌在乳腺癌中的肿瘤免疫影响

The onco-immunological implications of Fusobacterium nucleatum in breast cancer.

作者信息

Van der Merwe Michelle, Van Niekerk Gustav, Botha Alf, Engelbrecht Anna-Mart

机构信息

Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.

Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.

出版信息

Immunol Lett. 2021 Apr;232:60-66. doi: 10.1016/j.imlet.2021.02.007. Epub 2021 Feb 26.

Abstract

Breast cancer is a leading cause of death worldwide and a better understanding of this disease is needed to improve treatment outcomes. Recent evidence indicates that bacterial dysbiosis is associated with breast cancer, but the bacteria involved remain poorly characterised. Furthermore, an association between periodontal disease, characterised by oral dysbiosis, and breast cancer have also been discovered, but the mechanisms responsible for this association remains to be elucidated. The oral bacterium involved in periodontal disease, Fusobacterium nucleatum, have recently been detected in human breast tumour tissue and it promoted tumour growth and metastatic progression in a mouse model. The mechanisms of how F. nucleatum might colonise breast tissue and how it might promote tumour progression has not been fully elucidated yet. Here we discuss the breast tumour microbiota, its colonisation by F. nucleatum, possible mechanisms by which F. nucleatum might promote breast cancer progression and how this might impact breast cancer treatment. Literature indicates that F. nucleatum might promote breast cancer progression through activating the Toll-like receptor 4 pathway and by supressing the immune system. This results in cell growth and treatment resistance through autophagy as well as immune evasion. Targeted treatment directed at F. nucleatum combined with immunotherapy and autophagy inhibitors might therefore be a feasible treatment strategy for breast cancer patients.

摘要

乳腺癌是全球主要的死亡原因之一,需要更好地了解这种疾病以改善治疗效果。最近的证据表明,细菌失调与乳腺癌有关,但其中涉及的细菌仍未得到充分表征。此外,以口腔失调为特征的牙周病与乳腺癌之间的关联也已被发现,但这种关联的机制仍有待阐明。最近在人类乳腺肿瘤组织中检测到参与牙周病的口腔细菌具核梭杆菌,并且它在小鼠模型中促进了肿瘤生长和转移进展。具核梭杆菌如何在乳腺组织中定殖以及如何促进肿瘤进展的机制尚未完全阐明。在这里,我们讨论乳腺肿瘤微生物群、具核梭杆菌对其的定殖、具核梭杆菌可能促进乳腺癌进展的机制以及这可能如何影响乳腺癌治疗。文献表明,具核梭杆菌可能通过激活Toll样受体4途径和抑制免疫系统来促进乳腺癌进展。这通过自噬以及免疫逃避导致细胞生长和治疗抗性。因此,针对具核梭杆菌的靶向治疗与免疫疗法和自噬抑制剂相结合可能是乳腺癌患者的一种可行治疗策略。

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