Deciphering the Intricate Roles of Radiation Therapy and Complement Activation in Cancer.

Deciphering the Intricate Roles of Radiation Therapy and Complement Activation in Cancer.
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解释了放射治疗和癌症中补体激活的复杂作用。

DOI:
10.1016/j.ijrobp.2020.06.067
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发表时间:
2020-09-01
期刊:
International journal of radiation oncology, biology, physics
影响因子:
--
通讯作者:
Karam SD
Karam SD
中科院分区:
其他
文献类型:
--
作者:
Gadwa J;Karam SD

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补体系统由血清蛋白的集合组成,其充当先天免疫系统的主要前线效应臂。补体的激活可以通过单独的诱导途径发生:经典途径、甘露糖结合凝集素途径和替代途径。激活导致调理作用,通过称为过敏毒素的强效免疫介质募集效应细胞,以及通过形成膜攻击复合物(MAC)溶解细胞。需要补体的严格调节以防止补体级联的不适当激活。肿瘤微环境中的补体激活不会增加抗肿瘤作用,相反,它会促进肿瘤生长和疾病进展。放射治疗(RT)是治疗恶性肿瘤的主要手段,通过直接DNA损伤和免疫细胞的流入来控制肿瘤生长,重塑TME的组成。在TME中RT和补体活性之间的关系充其量是不确定的。下面的综述将集中在补体激活和RT的免疫调节作用的复杂相互作用,以及对肿瘤进展的总体影响。补体激活在癌症中的临床意义,以及治疗方法和潜在生物标志物的使用也将包括在内。
The complement system consists of a collection of serum proteins, which act as the main frontline effector arm of the innate immune system. Activation of complement can occur through the individual induction pathways: the classical, mannose-binding lectin, and alternative pathways. Activation results in opsonization, recruitment of effector cells through potent immune mediators known as anaphylatoxins, and cell lysis via the formation of the membrane attack complex (MAC). Stringent regulation of complement is required to protect against the inappropriate activation of the complement cascade. Complement activation within the tumor microenvironment does not increase anti-tumoral action, instead it enhances tumor growth and disease progression. Radiation therapy (RT) is a staple in treatment of malignancies and controls tumor growth through direct DNA damage and the influx of immune cells, reshaping the makeup of the TME. The relationship between RT and complement activity in the TME is uncertain at best. The following review will focus on the complex interaction of complement activation and the immune modulating effects of RT, and the overall effect on tumor progression. The clinical implications of complement activation in cancer, and the use of therapeutics and potential biomarkers will also be covered.
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