Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James's Hospital, Dublin 8, Ireland.
Adv Exp Med Biol. 2020;1231:1-12. doi: 10.1007/978-3-030-36667-4_1.
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 pro-inflammatory 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 anti-tumor immunity, and therefore an unsuitable therapeutic target in inflammation. The 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.
CX3CL1（趋化因子 Fractalkine）是一种多功能炎症趋化因子，具有单一受体 CX3CR1。CX3CL1 对周围细胞产生的生物学效应因多种因素而异，包括其结构、CX3CR1 的表达模式和细胞类型。例如，CX3CL1 的跨膜形式主要作为黏附分子，但当被切割成可溶性形式时，CX3CL1 主要作为趋化细胞因子发挥作用（图 1.1）。然而，CX3CL1 的生物学功能还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使 CX3CL1:CX3CR1 轴成为多种炎症性疾病的核心参与者，并使该趋化因子途径成为潜在的治疗靶点。然而，该趋化因子途径在效应记忆细胞毒性 T 细胞群体中的维持作用表明其作为抗病毒和抗肿瘤免疫的关键趋化因子，因此在炎症中不是一个合适的治疗靶点。CX3CL1 作为细胞毒性 T 细胞介导的免疫的关键调节剂的作用已得到多项研究的证实，这些研究表明 CX3CL1 是 TIL 募集趋化因子，也是结直肠癌、乳腺癌和肺癌的阳性预后因素。这些报告与大量表明 CX3CL1 在多种血液和实体恶性肿瘤中具有促肿瘤发生和促转移作用的研究相矛盾。本章将综述 CX3CL1 的独特结构、功能和生物学特性，并探讨其在免疫系统和肿瘤微环境中的生物学效应的多样性。总的来说，本章强调了我们只是触及了 CX3CL1 能力的表面，并表明必须进行更深入和更具机制性的研究，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。
