CX3CR1 and malignant progression of glioma

The varying period of time before an indolent low-grade glioma (LGG) inexorably transforms into a high-grade glioma (HGG) provides a unique opportunity for intervention. While recent clinical trials have demonstrated a clear survival benefit with early treatment of LGGs rather than watchful waiting, there is still a need to identify prognostic molecular markers that predict malignant transformation [1,2]. Although LGGs are often diagnosed in younger patients, as patients age, genetic instability and other changes in the tumor microenvironment can promote malignant progression to HGG. The driver mutations that define LGGs are well-established; however, genetic alterations that mediate recurrence and malignant transformation are essentially stochastic [3]. Therefore, identifying key shapers of the tumor microenvironment, rather than tumor-specific events, may provide a more consistent prognostic information and better therapeutic targets. In particular, tumor associated microglia and macrophages (TAMs) are immunosuppressive and proangiogenic, impeding effector anti-tumor lymphocyte responses and supporting invasion and growth of gliomas. Their pivotal role in malignant transformation of LGGs are only recently beginning to be understood.