Glioblastoma (GBM) is the deadliest and most aggressive neuroepithelial cancer of the central nervous system (CNS) with an abysmal median survival of 14.6-month despite the multiple forms of intervention. In the United States, the total annual incidence rate of glioma has been ~6 cases per 100,000 individuals, of which GBM accounts for about 50% of the cases, with a higher predominance in males. Clinical studies have indicated that most of the GBM patients present an intact blood–brain barrier (BBB) for certain brain regions, capable of blocking the delivery of agents to cancer sites. The BBB is considered to prevent diffusion of 98% of small-molecule and 100% of large-molecule agents into the brain from blood circulation. Given the aggressive and heterogeneous nature of GBM and the blocking capability of BBB, a very limited number of medications for patients with GBM is available in clinics. In addition, due to the existence of other cellular and extracellular barriers, as well as the development of drug resistance over the treatment course, the efficacy of many current therapeutic approaches has been compromised.

       Currently available standards of care for GBM include maximal tumor resection followed by radiotherapy, chemotherapy, and corticosteroids, all of which have immune suppressive characteristics. Unfortunately, complete surgical removal of the whole tumor is almost impossible due to their diffusive characteristics into normal brain tissue. Some reports indicated that ~65% of the post-surgery cases still showed residual tumor cells, which eventually contributed to a high relapse rate of GBM . Therefore, GBM patients may undergo repeated surgical resection, radiotherapy, chemotherapy, or additional bevacizumab treatment. Eventually, most of the patients suffering from GBM will relapse despite an ample set of interventional approaches. According to the data from Surveillance and Epidemiology, the median overall survival (OS) of GBM patients was normally less than 2 years from the time of first progression or relapse. An international phase III randomized trial, conducted by the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC), has shown that the median OS of GBM patients who received radiotherapy and Temozolomide therapy remains poor (14.6 months). Moreover, Grossman and colleagues found that the utilization of systemic chemotherapy and hyperfractionated radiation therapy with corticosteroids is likely to disable immune activity. Immune-suppressive characteristics, high toxicity, and lower OS of traditional care made a considerable number of GBM patients (~50%) not accept any second-line of anti-tumor treatment. In addition, there is no evidence that traditional intervention can significantly impact the OS rate under a recurrence setting. Accordingly, given the poor prognosis and limited therapy regimens for patients affected by GBM, there is an urgent need to develop novel therapeutic approaches.

This entry provides up-to-date knowledge on current state, challenges, and future perspectives on immunotherapy for glioblastoma.