Systemic Immune Bias Delineates Malignant Astrocytoma Survival Cohorts
| Autor: | David W. Andrews, Mark T. Curtis, Lawrence C. Kenyon, Jonathan Gorky, James S. Schwaber, Rhonda B. Kean, Aurore Lebrun, Larry Harshyne, Michael Prosniak, D. Craig Hooper |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Necrosis Carcinogenesis Immunology Astrocytoma medicine.disease_cause Cohort Studies 03 medical and health sciences 0302 clinical medicine Immune system Th2 Cells Cancer Survivors Glioma Genotype Tumor-Associated Macrophages medicine Immunology and Allergy Humans Th1-Th2 Balance Mutation business.industry Extracellular vesicle Middle Aged Th1 Cells medicine.disease Isocitrate Dehydrogenase Isocitrate dehydrogenase Cancer research Cytokines Female medicine.symptom business Glioblastoma 030215 immunology Anaplastic astrocytoma |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 206(7) |
| ISSN: | 1550-6606 |
| Popis: | Patients with grade III anaplastic astrocytomas (AA) separate into survival cohorts based on the presence or absence of mutations in isocitrate dehydrogenase (IDH). Progression to glioblastoma (GBM), morphologically distinguishable by elevated microvascular proliferation, necrosis, and cell division in tumor tissues, is considerably more rapid in IDH wild-type tumors such that their diagnosis as AA is relatively rare. More often initially presenting as GBM, these contain higher numbers of tumor-associated macrophages (TAMs) than most AA, and GBM patients also have higher levels of circulating M2 monocytes. TAM and M2 monocytes share functional properties inhibitory for antitumor immunity. Yet, although there is a wealth of data implicating TAM in tumor-immune evasion, there has been limited analysis of the impact of the circulating M2 monocytes. In the current study, immune parameters in sera, circulating cells, and tumor tissues from patients with primary gliomas morphologically diagnosed as AA were assessed. Profound differences in serum cytokines, glioma extracellular vesicle cross-reactive Abs, and gene expression by circulating cells identified two distinct patient cohorts. Evidence of type 2–immune bias was most often seen in patients with IDH wild-type AA, whereas a type 1 bias was common in patients with tumors expressing the IDH1R132H mutation. Nevertheless, a patient’s immune profile was better correlated with the extent of tumor vascular enhancement on magnetic resonance imaging than IDH mutational status. Regardless of IDH genotype, AA progression appears to be associated with a switch in systemic immune bias from type 1 to type 2 and the loss of tumor vasculature integrity. |
| Databáze: | OpenAIRE |
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