title: Exploring the role of inflammation in the malignant transformation of low-grade gliomas.
abstract: Studies of inflammatory mediators have established the tumor micro-environment as a driver of oncogenesis. This inflammatory milieu often precedes cancer, however recent data also point to the ability of oncogenic changes to induce inflammatory responses that are later harnessed by the tumor to survive and proliferate. In this review, we propose that the IDH1 mutation, present in the majority of low-grade gliomas (LGGs), initiates an inflammatory cascade that is ultimately hijacked by the tumor. Glioma infiltrating macrophages and microglia (GIMs) are polarized to the M2 phenotype, subverting the host's adaptive immune response, and fostering a tumor milieu ripe for angiogenesis, migration, and metastasis. As data continue to expand the role of inflammation in low-grade gliomas, new molecular pathways may emerge as therapeutic targets that offer a window of opportunity to intervene before the malignant transformation (MT) of LGGs occurs.
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Michelson
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
authors.forename: Jordina
authors.initials: J
authors.lastname: Rincon-Torroella
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, United States. Electronic address: jpgreenf@med.cornell.edu.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Greenfield
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000150:complications*; D018450:Disease Progression; D004660:Encephalitis / Q000209:etiology*; D005910:Glioma / Q000150:complications*; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism
keywords: IDH1 mutation; Inflammation; Low-grade gliomas; Macrophages; Malignant transformation; Microglia