Microglia/Macrophages Activation Status In Diffuse Gliomas

Diffuse gliomas are primary brain tumors characterized by infiltrative growth and high heterogeneity, which renders the disease mostly incurable. Advances in genetic analysis have characterized molecular and epigenetic alterations leading to impact on patients’ overall survival and clinical outcome, particularly in glioblastoma (GBM). However, glioma tumorigenicity is not controlled uniquely by its genetic alterations. The crosstalk between tumor cells and the surrounding microenvironment plays a crucial role in modulating glioma growth and aggressiveness. The most abundant non-neoplastic cells in this microenvironment belong to the myeloid lineage, comprising resident microglia, with central nervous system (CNS)-tailored functions, and infiltrating monocytes/macrophages from the bone marrow. Understanding the dynamics between tumor and myeloid cells and the correlation between oncogenic molecular alterations in the tumor and the inflammatory activation status of innate immunity cells would elucidate potential treatment alternatives. Our large cohort of human glioma consisted of both astrocytoma and oligodendroglioma tumors, ranging from grades II to IV. Using high-throughput DNA sequencing and immunohistochemistry, we have classified GBM samples in proneural, classical and mesenchymal. Next, we evaluated the activation status of microglia/macrophages within these samples. Despite the great heterogeneity, we observed higher levels of myeloid markers (IBA1, CD11b and CD68) in astrocytic tumors compared to oligodendrocytic ones and to non-neoplastic (NN) tissue. Anti-inflammation markers, such as CD163, are also more abundant in astrocytomas, as well as in the mesenchymal and classical GBM subtypes, while pro-inflammation markers, such as IL1-beta, show a more widespread expression throughout samples. Our preliminary data suggests an immune-suppressive and growth supportive characteristic for tumors with worse clinical outcome, linked to an activation profile of myeloid cells. Further exploring the characteristics and dynamics of innate immune cells within the microenvironment of different grades and subtypes of glioma is crucial for the better understanding of the disease progression. Citation Format: Thais F. Galatro, Paula Sola, Sueli M. Oba-Shinjo, Bart J. Eggen, Suely K. Marie. Microglia/macrophages activation status in diffuse gliomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3229.