Increased immune gene expression and immune cell infiltration in high-grade astrocytoma distinguish long-term from short-term survivors

Andrew M. Donson, Diane K. Birks, Stephanie A. Schittone, Bette K. Kleinschmidt-DeMasters, Derrick Y. Sun, Molly F. Hemenway, Michael H. Handler, Allen E. Waziri, Michael Wang, Nicholas K. Foreman

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Survival in the majority of high-grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGAwould aid development of more effective therapy and survival prediction. Factors associated with long-term survival have not been extensively studied using unbiased genome-wide expression analyses. In the current study, gene expression microarray profiles of HGA from long-term survivors were interrogated for discovery of survival-associated biological factors. Ontology analyses revealed that increased expression of immune function-related genes was the predominant biological factor that positively correlated with longer survival. A notable T cell signature was present within this prognostic immune gene set. Using immune cell-specific gene classifiers, both T cell-associated and myeloid linage-associated genes were shown to be enriched in HGA from long-term versus short-term survivors. Association of immune function and cell-specific genes with survival was confirmed independently in a larger publicly available glioblastoma gene expression microarray data set. Histology was used to validate the results of microarray analyses in a larger cohort of long-term survivors of HGA. Multivariate analyses demonstrated that increased immune cell infiltration was a significant independent variable contributing to longer survival, as was Karnofsky/Lansky performance score. These data provide evidence of a prognostic anti-tumor adaptive immune response and rationale for future development of immunotherapy in HGA.

Original languageEnglish (US)
Pages (from-to)1920-1927
Number of pages8
JournalJournal of Immunology
Volume189
Issue number4
DOIs
StatePublished - Aug 15 2012
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Donson, A. M., Birks, D. K., Schittone, S. A., Kleinschmidt-DeMasters, B. K., Sun, D. Y., Hemenway, M. F., Handler, M. H., Waziri, A. E., Wang, M., & Foreman, N. K. (2012). Increased immune gene expression and immune cell infiltration in high-grade astrocytoma distinguish long-term from short-term survivors. Journal of Immunology, 189(4), 1920-1927. https://doi.org/10.4049/jimmunol.1103373