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

• Published in: The Journal of immunology (1950) 2012-08, Vol.189 (4), p.1920-1927
• Main Authors: Donson, Andrew M, Birks, Diane K, Schittone, Stephanie A, Kleinschmidt-DeMasters, Bette K, Sun, Derrick Y, Hemenway, Molly F, Handler, Michael H, Waziri, Allen E, Wang, Michael, Foreman, Nicholas K
• Format: Article
• Language: English
• Subjects: Astrocytoma - genetics; Astrocytoma - immunology; Astrocytoma - mortality; Brain Neoplasms - genetics; Brain Neoplasms - immunology; Brain Neoplasms - mortality; Gene Expression Profiling; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Karnofsky Performance Status; Lymphocytes, Tumor-Infiltrating - immunology; Oligonucleotide Array Sequence Analysis; Prognosis; Proportional Hazards Models; Survivors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1103373

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 HGA would 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.