Lee Sue Chin, Dacheux Mélanie A, Norman Derek D, Balázs Louisa, Torres Raul M, Augelli-Szafran Corinne E, Tigyi Gábor J
Department of Physiology, University of Tennessee Health Science Center; Memphis, TN 38163, USA.
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center; Memphis, TN 38163, USA.
Cancers (Basel). 2020 May 10;12(5):1202. doi: 10.3390/cancers12051202.
The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of this crosstalk between cancer cells and their TME is the bioactive lipid lysophosphatidic acid (LPA). High levels of LPA and the enzyme generating it, termed autotaxin (ATX), are present in many cancers. It is also well documented that LPA drives tumor progression by promoting angiogenesis, proliferation, survival, invasion and metastasis. One of the hallmarks of cancer is the ability to modulate and escape immune detection and eradication. Despite the profound role of LPA in regulating immune functions and inflammation, its role in the context of tumor immunity has not received much attention until recently where emerging studies highlight that this signaling axis may be a means that cancer cells adopt to evade immune detection and eradication. The present review aims to look at the immunomodulatory actions of LPA in baseline immunity to provide a broad understanding of the subject with a special emphasis on LPA and cancer immunity, highlighting the latest progress in this area of research.
肿瘤微环境(TME)或许可以被最好地概念化为一个生态系统,该系统由癌细胞与多种基质成分相互作用构成,这些基质成分包括细胞外基质(ECM)、血液和淋巴网络、成纤维细胞、脂肪细胞以及免疫系统细胞。癌细胞与其TME之间这种相互作用的核心是生物活性脂质溶血磷脂酸(LPA)。许多癌症中都存在高水平的LPA及其生成酶——自分泌运动因子(ATX)。同样有充分文献记载,LPA通过促进血管生成、增殖、存活、侵袭和转移来推动肿瘤进展。癌症的一个标志是能够调节并逃避免疫检测和清除。尽管LPA在调节免疫功能和炎症方面具有重要作用,但直到最近,其在肿瘤免疫背景下的作用才受到较多关注,新出现的研究强调这个信号轴可能是癌细胞用来逃避免疫检测和清除的一种方式。本综述旨在探讨LPA在基础免疫中的免疫调节作用,以全面了解该主题,特别强调LPA与癌症免疫,突出这一研究领域的最新进展。