Glioblastoma ("GBM") is among the most common and most aggressive malignant primary brain tumors in humans, accounting for approximately 12% to 15% of all cases. While brain cancer has many potential risk factors, including smoking and alcohol consumption, researchers have also identified a possible link between GBM and various pathogenic infections such as cytomegalovirus ("CMV").
Numerous previous studies have confirmed that CMV nucleic acids and genes are present in more than 90% of some GBM tumors. A new study led by researchers at the California Pacific Medical Center expands on existing research and published articles and explores the connection between CMV and glioma stem-like cells ("GSC"). According to the study’s authors, existing data supports the idea that long-term, low-level CMV infection may promote the survival, stemness, and proliferation of glioma stem-like cells and could significantly contribute to GBM pathogenesis.Glioma stem-like cells, like some other malignant tumors, exhibit features of self-renewal and have the ability to initiate and sustain tumor growth, metastasis, and resistance to therapy. Glioma stem-like cells are characterized by resistance to radiation and chemotherapy and are primarily responsible for GBM recurrence.
Based on the hypothesis that a specific CMV gene signature may be associated with GBM pathogenesis, study researchers used glioma cell lines and primary glioma stem-like cells infected with clinical and laboratory CMV strains, and measured relative viral gene expression levels along several time lines, up to 15 weeks post-infection.
Researchers concluded that while CMV gene expression was detected in several infected glioma lines through week five, only CMV-infected glioma stem-like cells expressed viral gene characteristics at the 15 week mark. A significant finding was that CMV-infected glioma stem-like cells outlived their uninfected counterparts, and this extended survival was paralleled by an increased frequency of tumor sphere formation and an increase in stemness regulators, including BMX, a novel CMV target first identified by the California Pacific Medical Center study.
Overall, the data support the theory that long-term, low-level CMV infection plays a critical role in the survival, stemness, and reproduction of glioma stem-like cells and could significantly contribute to GBM development and progression.
Researchers are continuing to study the relationship between CMV, GBM, and other types of cancer, including prostate, colon, and breast cancer. Clinical trials to evaluate the efficacy of CMV-specific cellular immunotherapy for GBM are also underway. With the increasing amount of evidence regarding the CMV-GBM connection, there is also growing interest in exploring vaccination against CMV antigens as a component of emerging immunotherapeutic strategies against GBMs and other malignant tumors.