Tumor Microenvironment and Microvascular Density in Human Glioblastoma

Abstract

Glioblastoma (GBM) is a very aggressive form of cancer affecting the central nervous system. Although it occurs almost exclusively in the brain, glioblastoma can also appear in the brainstem, cerebellum, and spinal cord. It is characterized by high rates of proliferation, invasion, and necrosis. Moreover, GBM is a highly vascularized tumor and presents resistance to therapy. Recent data indicate that GBM cells are surrounded by a microenvironment (TME) which includes a complex network constituted of cellular/extracellular components and vessels able to influence both tumor growth and angiogenesis. In this retrospective study, we evaluated 30 bioptic specimens of adult patients diagnosed with IDH1 wild type GBM taken at the time of the first diagnosis. Each section has been divided into two experimental zones: the tumor side and the healthy surrounding tissue. We performed a series of immunohistochemical stainings with the purpose of evaluating the presence of total and M2 macrophages, CD4+-, CD8+-lymphocytes, and CD34+ microvessels. In addition, we have also evaluated the percentage of cells expressing bcl6 and p53 to determine any possible correlations with TME. Our data showed a significant increase in the total and M2 type macrophages, of CD4+ and CD8+ lymphocytes, and of CD34+ microvessels in the tumoral area respective to the healthy zone. We also confirmed our previous data showing the higher number of p53 and BCL6+ cells in the tumor area with a positive correlation between BCL6 and CD34+ microvessels. In conclusion, the data that came from this work support the important role played by microenvironment components in GBM progression. These results could contribute to the generation of new specific therapies useful in preventing GBM progression.

Keywords

• angiogenesis
• BCL-6
• glioblastoma
• lymphocytes
• macrophages
• tumor microenvironment