Abstract
Simple SummaryGlioblastoma is the most common primary brain tumor in adults, and its aggressive nature yields a poor prognosis despite current treatment strategies. The aim of our literature review is to discuss various immunotherapeutic strategies currently being investigated in the treatment of glioblastoma. Checkpoint inhibitors, various vaccination strategies, and CAR T-cell therapies serve as some of the most investigated immunotherapeutic strategies. However, all strategies face various limitations, such as the low relative mutational burden, the immunosuppressive tumor microenvironment, and genetic heterogeneity, which serve as the current challenges.Glioblastoma (GBM) is a lethal primary brain tumor. Despite extensive effort in basic, translational, and clinical research, the treatment outcomes for patients with GBM are virtually unchanged over the past 15 years. GBM is one of the most immunologically “cold” tumors, in which cytotoxic T-cell infiltration is minimal, and myeloid infiltration predominates. This is due to the profound immunosuppressive nature of GBM, a tumor microenvironment that is metabolically challenging for immune cells, and the low mutational burden of GBMs. Together, these GBM characteristics contribute to the poor results obtained from immunotherapy. However, as indicated by an ongoing and expanding number of clinical trials, and despite the mostly disappointing results to date, immunotherapy remains a conceptually attractive approach for treating GBM. Checkpoint inhibitors, various vaccination strategies, and CAR T-cell therapy serve as some of the most investigated immunotherapeutic strategies. This review article aims to provide a general overview of the current state of glioblastoma immunotherapy. Information was compiled through a literature search conducted on PubMed and clinical trials between 1961 to 2021.
Highlights
Glioblastoma (GBM) is the most malignant of the glial tumors and represents more than half of all primary brain tumors in the United States, with an annual prevalence of roughly 3.19 per 100,000 people [1,2]
The Stupp protocol entails the administration of temozolomide (TMZ) (75 mg/m2 ) with concomitant radiotherapy (RT) (60 Gy) for 42 days followed by six cycles of adjuvant TMZ (150 to 200 mg/m2 ) administered for five days during each 28-day cycle [8]
CheckMate 143 served as the first randomized phase I clinical trial that targeted the PD pathway in recurrent
Summary
Glioblastoma (GBM) is the most malignant of the glial tumors (grade IV) and represents more than half of all primary brain tumors in the United States, with an annual prevalence of roughly 3.19 per 100,000 people [1,2]. A poor response to existing treatment is usually seen due to the inherent intra-tumor heterogeneity [4,5,6]. The median survival of patients with GBM is approximately 14 months, even with aggressive treatment regimens [2,7]. The Stupp protocol remains the standard of care for GBM, with virtually no improvements since it was developed in 2005. The Stupp protocol entails the administration of temozolomide (TMZ) (75 mg/m2 ) with concomitant radiotherapy (RT) (60 Gy) for 42 days followed by six cycles of adjuvant TMZ (150 to 200 mg/m2 ) administered for five days during each 28-day cycle [8]. In 2017, tumor-treating fields and maintenance temozolomide were shown to increase progression-free survival and overall survival in patients when compared to maintenance temozolomide alone [9].
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