Molecular Neurobiology Laboratory, The Salk Institute, San Diego, CA 92037, USA.
Mediators Inflamm. 2012;2012:568783. doi: 10.1155/2012/568783. Epub 2012 Dec 18.
The interaction between tumor progression and innate immune system has been well established in the last years. Indeed, several lines of clinical evidence indicate that immune cells such as tumor-associated macrophages (TAMs) interact with tumor cells, favoring growth, angiogenesis, and metastasis of a variety of cancers. In most tumors, TAMs show properties of an alternative polarization phenotype (M2) characterized by the expression of a series of chemokines, cytokines, and proteases that promote immunosuppression, tumor proliferation, and spreading of the cancer cells. Tumor suppressor genes have been traditionally linked to the regulation of cancer progression; however, a growing body of evidence indicates that these genes also play essential roles in the regulation of innate immunity pathways through molecular mechanisms that are still poorly understood. In this paper, we provide an overview of the immunobiology of TAMs as well as what is known about tumor suppressors in the context of immune responses. Recent advances regarding the role of the tumor suppressor ARF as a regulator of inflammation and macrophage polarization are also reviewed.
近年来,肿瘤进展与固有免疫系统之间的相互作用已得到充分证实。事实上,有几条临床证据表明,免疫细胞(如肿瘤相关巨噬细胞[TAMs])与肿瘤细胞相互作用,促进多种癌症的生长、血管生成和转移。在大多数肿瘤中,TAMs 表现出一种替代性极化表型(M2)的特征,其特征是表达一系列趋化因子、细胞因子和蛋白酶,促进免疫抑制、肿瘤增殖和癌细胞的扩散。肿瘤抑制基因传统上与癌症进展的调节有关;然而,越来越多的证据表明,这些基因在调节固有免疫途径方面也起着至关重要的作用,其分子机制尚不清楚。在本文中,我们概述了 TAMs 的免疫生物学,以及在免疫反应背景下肿瘤抑制因子的已知情况。还回顾了肿瘤抑制因子 ARF 作为炎症和巨噬细胞极化调节剂的最新进展。