Wrzesinski Stephen H, Wan Yisong Y, Flavell Richard A
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5262-70. doi: 10.1158/1078-0432.CCR-07-1157.
Immune homeostasis is a delicate balance between the immune defense against foreign pathogens and suppression of the immune system to maintain self-tolerance and prevent autoimmune disease. Maintenance of this balance involves several crucial networks of cytokines and various cell types. Among these regulators, transforming growth factor-beta (TGF-beta) is a potent cytokine with diverse effects on hematopoietic cells. Its pivotal function within the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis and activation of leukocytes in the periphery, including lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. Through its pleiotropic effects on these immune cells, TGF-beta prevents the development of autoimmune diseases without compromising immune responses to pathogens. However, overactivation of this pathway can lead to several immunopathologies under physiologic conditions including cancer progression, making it an attractive target for antitumor therapies. This review discusses the biological functions of TGF-beta and its effects on the immune system and addresses how immunosuppression by this cytokine can promote tumorigenesis, providing the rationale for evaluating the immune-enhancing and antitumor effects of inhibiting TGF-beta in cancer patients.
免疫稳态是对外来病原体的免疫防御与免疫系统抑制之间的微妙平衡，以维持自身耐受性并预防自身免疫性疾病。维持这种平衡涉及细胞因子的几个关键网络和各种细胞类型。在这些调节因子中，转化生长因子-β（TGF-β）是一种对造血细胞具有多种作用的强效细胞因子。它在免疫系统中的关键功能是通过调节淋巴细胞的增殖、分化和存活来维持耐受性。此外，TGF-β通过调节趋化作用和外周血白细胞（包括淋巴细胞、自然杀伤细胞、树突状细胞、巨噬细胞、肥大细胞和粒细胞）的激活来控制炎症反应的起始和消退。通过对这些免疫细胞的多效性作用，TGF-β在不损害对病原体的免疫反应的情况下预防自身免疫性疾病的发展。然而，在生理条件下，该途径的过度激活可导致包括癌症进展在内的多种免疫病理，使其成为抗肿瘤治疗的有吸引力的靶点。本综述讨论了TGF-β的生物学功能及其对免疫系统的影响，并探讨了这种细胞因子的免疫抑制如何促进肿瘤发生，为评估抑制TGF-β对癌症患者的免疫增强和抗肿瘤作用提供了理论依据。
