Comen Elizabeth A, Bowman Robert L, Kleppe Maria
Breast Cancer Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Center for Hematopoietic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Front Cell Dev Biol. 2018 Jun 12;6:56. doi: 10.3389/fcell.2018.00056. eCollection 2018.
Historically, the link between chronic inflammation and cancer has long been speculated. Only more recently, pre-clinical and epidemiologic data as well as clinical evidence all point to the role of the tumor microenvironment as inextricably connected to the neoplastic process. The tumor microenvironment (TME), a complex mix of vasculature, inflammatory cells, and stromal cells is the essential "soil" helping to modulate tumor potential. Increasingly, evidence suggests that chronic inflammation modifies the tumor microenvironment, via a host of mechanisms, including the production of cytokines, pro-inflammatory mediators, angiogenesis, and tissue remodeling. Inflammation can be triggered by a variety of different pressures, such as carcinogen exposure, immune dysfunction, dietary habits, and obesity, as well as genetic alterations leading to oncogene activation or loss of tumor suppressors. In this review, we examine the concept of the tumor microenvironment as related to both extrinsic and intrinsic stimuli that promote chronic inflammation and in turn tumorigenesis. Understanding the common pathways inherent in an inflammatory response and the tumor microenvironment may shed light on new therapies for both primary and metastatic disease. The concept of personalized medicine has pushed the field of oncology to drill down on the genetic changes of a cancer, in the hopes of identifying individually targeted agents. Given the complexities of the tumor microenvironment, it is clear that effective oncologic therapies will necessitate targeting not only the cancer cells, but their dynamic relationship to the tumor microenvironment as well.
从历史上看，慢性炎症与癌症之间的联系早已为人所推测。直到最近，临床前和流行病学数据以及临床证据均表明肿瘤微环境与肿瘤形成过程有着千丝万缕的联系。肿瘤微环境（TME）是血管、炎症细胞和基质细胞的复杂组合，是调节肿瘤潜能的关键“土壤”。越来越多的证据表明，慢性炎症通过多种机制改变肿瘤微环境，这些机制包括细胞因子的产生、促炎介质、血管生成和组织重塑。炎症可由多种不同压力引发，如致癌物暴露、免疫功能障碍、饮食习惯和肥胖，以及导致癌基因激活或肿瘤抑制因子缺失的基因改变。在本综述中，我们探讨了肿瘤微环境的概念，它与促进慢性炎症进而引发肿瘤发生的外在和内在刺激因素相关。了解炎症反应和肿瘤微环境中固有的共同途径，可能会为原发性和转移性疾病的新疗法提供线索。精准医学的概念推动肿瘤学领域深入研究癌症的基因变化，以期找到个体化的靶向药物。鉴于肿瘤微环境的复杂性，显然有效的肿瘤治疗不仅需要靶向癌细胞，还需要针对它们与肿瘤微环境的动态关系。
