Department of Pathology, VU University Medical Center/Cancer Center Amsterdam, Amsterdam, Zuid Holland 1081 HV The Netherlands.
J Leukoc Biol. 2009 Nov;86(5):1075-87. doi: 10.1189/jlb.0309147. Epub 2009 Sep 10.
ABC transporters were identified originally for their contribution to clinical MDR as a result of their capacity to extrude various unrelated cytotoxic drugs. More recent reports have shown that ABC transporters can play important roles in the development, differentiation, and maturation of immune cells and are involved in migration of immune effector cells to sites of inflammation. Many of the currently identified, endogenous ABC transporter substrates have immunostimulating effects. Increasing the expression of ABC transporters on immune cells and thereby enhancing immune cell development or functionality may be beneficial to immunotherapy in the field of oncology. On the contrary, in the treatment of autoimmune diseases, blockade of these transporters may prove beneficial, as it could dampen disease activity by compromising immune effector cell functions. This review will focus on the expression, regulation, and substrate specificity of ABC transporters in relation to functional activities of immune effector cells and discusses implications for the treatment of cancer on the one hand and autoimmune diseases on the other.
ABC 转运蛋白最初因其能够排出各种不相关的细胞毒性药物而对临床 MDR 的贡献而被识别。最近的报道表明，ABC 转运蛋白在免疫细胞的发育、分化和成熟中发挥着重要作用，并参与免疫效应细胞向炎症部位的迁移。目前已鉴定出的许多内源性 ABC 转运蛋白底物具有免疫刺激作用。增加免疫细胞上 ABC 转运蛋白的表达，从而增强免疫细胞的发育或功能，可能有益于肿瘤学领域的免疫治疗。相反，在治疗自身免疫性疾病时，阻断这些转运蛋白可能会证明是有益的，因为它可以通过损害免疫效应细胞的功能来减轻疾病活动。这篇综述将重点讨论 ABC 转运蛋白在免疫效应细胞的功能活动方面的表达、调节和底物特异性，并讨论其对癌症治疗一方面和自身免疫性疾病治疗另一方面的影响。
