Whiteside T L
University of Pittsburgh School of Medicine and The Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Oncogene. 2008 Oct 6;27(45):5904-12. doi: 10.1038/onc.2008.271.
The tumor microenvironment is created by the tumor and dominated by tumor-induced interactions. Although various immune effector cells are recruited to the tumor site, their anti-tumor functions are downregulated, largely in response to tumor-derived signals. Infiltrates of inflammatory cells present in human tumors are chronic in nature and are enriched in regulatory T cells (T(reg)) as well as myeloid suppressor cells (MSC). Immune cells in the tumor microenvironment not only fail to exercise antitumor effector functions, but they are co-opted to promote tumor growth. Sustained activation of the NF-kappaB pathway in the tumor milieu represents one mechanism that appears to favor tumor survival and drive abortive activation of immune cells. The result is tumor escape from the host immune system. Tumor escape is accomplished through the activation of one or several molecular mechanisms that lead to inhibition of immune cell functions or to apoptosis of anti-tumor effector cells. The ability to block tumor escape depends on a better understanding of cellular and molecular pathways operating in the tumor microenvironment. Novel therapeutic strategies that emerge are designed to change the pro-tumor microenvironment to one favoring acute responses and potent anti-tumor activity.
肿瘤微环境由肿瘤形成，并由肿瘤诱导的相互作用主导。尽管各种免疫效应细胞被募集到肿瘤部位，但其抗肿瘤功能大多因肿瘤衍生信号而下调。人类肿瘤中存在的炎性细胞浸润本质上是慢性的，且富含调节性T细胞（T(reg)）以及髓系抑制细胞（MSC）。肿瘤微环境中的免疫细胞不仅无法发挥抗肿瘤效应功能，反而被利用来促进肿瘤生长。肿瘤微环境中NF-κB通路的持续激活是一种似乎有利于肿瘤存活并驱动免疫细胞异常激活的机制。结果是肿瘤逃避免疫系统。肿瘤逃逸是通过激活一种或几种导致免疫细胞功能抑制或抗肿瘤效应细胞凋亡的分子机制来实现的。阻断肿瘤逃逸的能力取决于对肿瘤微环境中细胞和分子途径的更好理解。新出现的治疗策略旨在将促肿瘤微环境转变为有利于急性反应和强大抗肿瘤活性的微环境。
