Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment.

摘要: While treatment with surgery, radiotherapy and/or chemotherapy may prolong life for patients glioblastoma, recurrence is inevitable. What still being discovered how much these treatments and of disease affect the molecular profiles tumors adapt to withstand pressures. Understanding such changes will uncover pathways used by tumor evade destruction elucidate new targets development. Nineteen matched pre-treatment post-treatment glioblastoma were subjected gene expression profiling (Fluidigm, TaqMan assays), MGMT promoter methylation analysis (pyrosequencing) protein DNA repair pathways, known be involved in temozolomide resistance (immunohistochemistry). Gene molecularly subtype revealed that 26% recurrent specimens did not match their primary diagnostic specimen subtype. Post-treatment had which correlated mechanisms including increased APEX1 (p < 0.05) altered status. In addition, genes associated immune suppression, invasion aggression (GPNMB, CCL5, KLRC1) polarization toward an M2 phenotype (CD163 MSR1) up-regulated tumors, demonstrating overall change microenvironment favoring aggressive growth recurrence. This was confirmed vitro studies determined glioma cell migration enhanced presence polarized macrophage conditioned media. Further, macrophage-modulated markedly (temozolomide resistant) cells. These findings highlight ability glioblastomas only toxic onslaught therapy but also system suggesting immune-altering therapies value treating this terrible disease.