Gubernatorova Ekaterina O, Polinova Almina I, Petropavlovskiy Mikhail M, Namakanova Olga A, Medvedovskaya Alexandra D, Zvartsev Ruslan V, Telegin Georgij B, Drutskaya Marina S, Nedospasov Sergei A
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Cancers (Basel). 2021 Apr 8;13(8):1775. doi: 10.3390/cancers13081775.
Tumor necrosis factor (TNF) and lymphotoxin alpha (LTα) are two related cytokines from the TNF superfamily, yet they mediate their functions in soluble and membrane-bound forms via overlapping, as well as distinct, molecular pathways. Their genes are encoded within the major histocompatibility complex class III cluster in close proximity to each other. TNF is involved in host defense, maintenance of lymphoid tissues, regulation of cell death and survival, and antiviral and antibacterial responses. LTα, known for some time as TNFβ, has pleiotropic functions including control of lymphoid tissue development and homeostasis cross talk between lymphocytes and their environment, as well as lymphoid tissue neogenesis with formation of lymphoid follicles outside the lymph nodes. Along with their homeostatic functions, deregulation of these two cytokines may be associated with initiation and progression of chronic inflammation, autoimmunity, and tumorigenesis. In this review, we summarize the current state of knowledge concerning TNF/LTα functions in tumor promotion and suppression, with the focus on the recently uncovered significance of host-microbiota interplay in cancer development that may explain some earlier controversial results.
肿瘤坏死因子（TNF）和淋巴毒素α（LTα）是肿瘤坏死因子超家族中的两种相关细胞因子，然而它们通过重叠以及不同的分子途径以可溶性和膜结合形式介导其功能。它们的基因在主要组织相容性复合体III类簇中彼此紧密相邻编码。TNF参与宿主防御、淋巴组织维持、细胞死亡和存活调节以及抗病毒和抗菌反应。LTα，曾有一段时间被称为TNFβ，具有多效性功能，包括控制淋巴组织发育和淋巴细胞与其环境之间的稳态相互作用，以及在淋巴结外形成淋巴滤泡的淋巴组织新生。除了它们的稳态功能外，这两种细胞因子的失调可能与慢性炎症、自身免疫和肿瘤发生的起始和进展有关。在这篇综述中，我们总结了关于TNF/LTα在肿瘤促进和抑制中的功能的当前知识状态，重点关注宿主-微生物群相互作用在癌症发展中最近发现的意义，这可能解释了一些早期有争议的结果。
