Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.

The effects of radiation therapy (RT) for cancer can be systemic and partially mediated by the immune system. However, radiation alone is unlikely to transform an immunosuppressive environment into an immunostimulatory one. Therefore, an effective combination of radiation therapy and immunotherapy may provide a new more efficient treatment approach. Here we investigated how the expression of programmed cell death-ligand 1 (PD-L1) in the microenvironment of the tumor varied in different RT regimens with the same Biologically Effective Dose (BED). In this study, female BALB/c mice inoculated with CT26 tumor cells were irradiated with three different RT regimens using the same Biologically Effective Dose (BED) of 40 Gray (Gy). These included Ablative RT (1*15 Gy), Hypo-fractionated RT (2*10 Gy), and Conventional RT (10*3 Gy). PD-L1 expression was analyzed with immunohistochemical staining on days 2, 20, and when the size of tumors had reached 2 cm2 after RT. All treated groups expressed PD-L1, but the group receiving single ablative high dose RT showed higher expression compared to the other groups. No significant differences in PD-L1 expression were observed at different times in the same group. These findings showed that different regimens of RT have different effects on the tumor microenvironment (TME), so a combination of RT and immune checkpoint blockade could be clinically used in cancer patients.

The effects of radiation therapy (RT) for cancer can be systemic and partially mediated by the immune system. However, radiation alone is unlikely to transform an immunosuppressive environment into an immunostimulatory one. Therefore, an effective combination of RT and immunotherapy may provide a new, more efficient treatment approach. Here, we investigated how the expression of programmed cell death-ligand 1 (PD-L1) in the tumor microenvironment varied in different RT regimens with the same biologically effective dose. In this study, female BALB/c mice inoculated with CT26 tumor cells were irradiated with 3 different RT regimens using the same BED of 40 gray (Gy). These included ablative RT (1*15 Gy), hypo-fractionated RT (2*10 Gy), and conventional (Hyper-fractionated) RT (10*3 Gy). PD-L1 expression was analyzed with immunohistochemical staining on days 2 and 20 and when the size of tumors had reached 2 cm2 after RT. All treated groups expressed PD-L1, but the group receiving single ablative high-dose RT showed higher expression compared to the other groups. No significant differences in PD-L1 expression were observed at different times in the same group. These findings showed that different regimens of RT have different effects on the TME, so a combination of RT and immune checkpoint blockade could be clinically used in cancer patients.