CX3CL1 Signaling in the Tumor Microenvironment
CX3CL1 Signaling in the Tumor Microenvironment
复制标题
DOI：
10.1007/978-3-030-36667-4_1
复制
发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Lysaght, Joanne
中科院分区：
文献类型：
--
作者：
Conroy, Melissa J.;Lysaght, Joanne
CX 3CL 1（Fractalkine）是一种多功能炎症趋化因子，具有单一受体CX 3CR 1。CX3CL1对周围细胞的生物学效应取决于许多因素，包括其结构，CX3CR1的表达模式和细胞类型。例如，CX3CL1的跨膜形式主要用作粘附分子，但当切割成可溶形式时，CX3CL1主要用作趋化细胞因子（图1.1）。然而，CX3CL1的生物学功能也延伸到免疫细胞的存活和保留。表达CX3CR1的免疫细胞的促炎性质将CX3CL1：CX3CR1轴作为多种炎性疾病的中心参与者，并将该趋化因子途径定位为潜在的治疗靶点。然而，该趋化因子途径在维持效应记忆细胞毒性T细胞群体中的新作用暗示其作为抗病毒和抗肿瘤免疫中的关键趋化因子，因此，CX3CL1作为细胞毒性T细胞介导的免疫的关键调节剂的不适当报道的作用得到了几项研究的支持，这些研究证明CX3CL1是结肠直肠癌中重要的TIL募集趋化因子和阳性预后因子，乳腺癌和肺癌。这些报告是冲突的大量研究表明，促肿瘤发生和促转移的作用，CX3CL1在多种血液和实体malignances.This章将审查独特的结构，功能和生物学的CX3CL1和解决的多样性，其在免疫系统和肿瘤微环境中的生物学效应。总的来说，本章强调了我们刚刚触及CX3CL1功能的表面，并建议必须进行进一步的深入和机制研究，包括所有CX3CL1相互作用，以充分了解其在癌症中的作用及其作为治疗靶点的潜力。
CX3CL1 (Fractalkine) is a multifunctional inflammatory chemokine with a single receptor CX3CR1. The biological effects elicited by CX3CL1 on surrounding cells vary depending on a number of factors including its structure, the expression pattern of CX3CR1, and the cell type. For instance, the transmembrane form of CX3CL1 primarily serves as an adhesion molecule, but when cleaved to a soluble form, CX3CL1 predominantly functions as a chemotactic cytokine (Fig. 1.1). However, the biological functions of CX3CL1 also extend to immune cell survival and retention. The proinflammatory nature of CX3CR1--expressing immune cells place the CX3CL1:CX3CR1 axis as a central player in multiple inflammatory disorders and position this chemokine pathway as a potential therapeutic target. However, the emerging role of this chemokine pathway in the maintenance of effector memory cytotoxic T cell populations implicates it as a key chemokine in anti-viral and antitumor immunity, and therefore an unsuitable reported role of CX3CL1 as a key regulator of cytotoxic T cell-mediated immunity is supported by several studies that demonstrate CX3CL1 as an important TIL-recruiting chemokine and a positive prognostic factor in colorectal, breast, and lung cancer. Such reports are conflicting with an overwhelming number of studies demonstrating a pro-tumorigenic and pro-metastatic role of CX3CL1 across multiple blood and solid malignancies.This chapter will review the unique structure, function, and biology of CX3CL1 and address the diversity of its biological effects in the immune system and the tumor microenvironment. Overall, this chapter highlights how we have just scratched the surface of CX3CL1's capabilities and suggests that further in-depth and mechanistic studies incorporating all CX3CL1 interactions must be performed to fully appreciate its role in cancer and its potential as a therapeutic target.