Systemic Immune Bias Delineates Malignant Astrocytoma Survival Cohorts.

Authors

• Michael Prosniak
• Larry A Harshyne
• Jonathan Gorky
• Mark T Curtis
• Lawrence C Kenyon
• James S Schwaber
• Aurore Lebrun
• Rhonda B Kean
• David W Andrews
• D Craig Hooper

Publication/Presentation Date

4-1-2021

Abstract

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.

Volume

206

Issue

7

First Page

1483

Last Page

1492

ISSN

1550-6606

Published In/Presented At

Prosniak, M., Harshyne, L. A., Gorky, J., Curtis, M. T., Kenyon, L. C., Schwaber, J. S., Lebrun, A., Kean, R. B., Andrews, D. W., & Hooper, D. C. (2021). Systemic Immune Bias Delineates Malignant Astrocytoma Survival Cohorts. Journal of immunology (Baltimore, Md. : 1950), 206(7), 1483–1492. https://doi.org/10.4049/jimmunol.2000901

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

33685995

Department(s)

Administration and Leadership

Document Type

Article