Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.
نویسندگان
چکیده
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.
منابع مشابه
Macrophages in Tumor Microenvironments and the Progression of Tumors
Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2...
متن کاملActivation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice.
During injury to the nervous system, innate immune cells mediate phagocytosis of debris, cytokine production, and axon regeneration. In the neuro-degenerative disease amyotrophic lateral sclerosis (ALS), innate immune cells in the CNS are activated. However, the role of innate immunity in the peripheral nervous system (PNS) has not been well defined. In this study, we characterized robust activ...
متن کاملHypoxia Potentiates Glioma-Mediated Immunosuppression
Glioblastoma multiforme (GBM) is a lethal cancer that exerts potent immune suppression. Hypoxia is a predominant feature of GBM, but it is unclear to the degree in which tumor hypoxia contributes to this tumor-mediated immunosuppression. Utilizing GBM associated cancer stem cells (gCSCs) as a treatment resistant population that has been shown to inhibit both innate and adaptive immune responses...
متن کاملP157: Periostin Recruits Tumor Associated Macrophages in Glioblastoma Multiform
Glioblastoma multiform (GBM) is the most common and lethal type of primary brain tumors with high rates of morbidity and mortality. Treatment options are limited and ineffective in most of the cases. Epidemiological studies have shown a link between inflammation and glioma genesis. In addition, at the molecular level, pro-inflammatory cytokines released from activated microglia can increa...
متن کاملCharacterization of tumor infiltrated cells in mouse model
Solid tumors show a trend to develop immunosuppressive microenvironment and a dynamic cell composition along tumor progression. Various types of non-immune and immune cells constitute solid tumor. Understanding the change of cellular constituents and their function is pertinent to understand tumor immune status, which enables rational design of cancer immunotherapy. Given the complexity of tumo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- JCI insight
دوره 1 2 شماره
صفحات -
تاریخ انتشار 2016