GBM immunotherapy: Exploring molecular and clinical frontiers.

GBM is the most common, aggressive, and intracranial primary brain tumor; it originates from the glial progenitor cells, has poor overall survival (OS), and has limited treatment options. In this decade, GBM immunotherapy is in trend and preferred over several conventional therapies, due to their better patient survival outcome. This review explores the clinical trials of several immunotherapeutic approaches (immune checkpoint blockers (ICBs), CAR T-cell therapy, cancer vaccines, and adoptive cell therapy) with their efficacy and safety. Despite significant progress, several challenges (viz., immunosuppressive microenvironment, heterogeneity, and blood-brain barrier (BBB)) were experienced that hamper their immunotherapeutic potential. Furthermore, these challenges were clinically studied to be resolved by multiple combinatorial approaches, discussed in the later part of the review. Thus, this review suggests the clinical use and potential of immunotherapy in GBM and provides the holistic recent knowledge and future perspectives.

Ghosh MK ，Kumar S ，Begam S ，Ghosh S ，Basu M ... -  《-》

A scientometric analysis of immunotherapies for gliomas: Focus on GBM.

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. The standard therapy for GBM has remained unchanged for nearly two decades, with no significant improvement in survival outcomes. Despite several barriers such as the tumor microenvironment (TME) and blood-brain barrier, immunotherapies bring new hope for the treatment of GBM. To better understand the development and progress of immunotherapies in GBM, we made this scientometric analysis of this field. A total of 3753 documents were obtained from the Web of Science Core Collection, with publication years ranging from 1999 to 2022. The Web of Science platform, CiteSpace, and VOS viewer were used to conduct the scientometric analysis. The results of scientometric analysis showed that this field has recently become a popular topic of interest. The United States had the most publications among 89 countries or regions. Keyword analysis indicated significant areas in the field of immunotherapies for GBM, especially TME, immune checkpoint blockades (ICBs), chimeric antigen receptor T (CAR-T) cells, vaccines, and oncolytic viruses (OVs). Overall, we hope that this scientometric analysis can provide insights for researchers and promote the development of this field.

Xing Y ，Yasinjan F ，Geng H ，He M ，Yang M ，Gao Y ，Zhang J ，Zhang L ，Guo B ... -  《-》

Current progress in chimeric antigen receptor T cell therapy for glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors with an unfavorable prognosis and overall survival of approximately 20 months following diagnosis. The current treatment for GBM includes surgical resections and chemo- and radiotherapeutic modalities, which are not effective. CAR-T immunotherapy has been proven effective for CD19-positive blood malignancies, and the application of CAR-T cell therapy for solid tumors including GBM offers great hope for this aggressive tumor which has a limited response to current treatments. CAR-T technology depends on the use of patient-specific T cells genetically engineered to express specific tumor-associated antigens (TAAs). Interaction of CAR-T cells with tumor cells triggers the destruction/elimination of these cells by the induction of cytotoxicity and the release of different cytokines. Despite the great promise of CAR-T cell-based therapy several challenges exist. These include the heterogeneity of GBM cancer cells, aberrant various signaling pathways involved in tumor progression, antigen escape, the hostile inhibitory GBM microenvironment, T cell dysfunction, blood-brain barrier, and defective antigen presentation. All need to be addressed before full application at the clinical level can begin. Herein we provide a focused review of the rationale for the use of different types of CAR-T cells (including FcγRs), the different GBM-associated antigens, the challenges still facing CAR-T-based therapy, and means to overcome such challenges. Finally, we enumerate currently completed and ongoing clinical trials, highlighting the different ways such trials are designed to overcome specific problems. Exploitation of the full potential of CAR-T cell therapy for GBM depends on their solution.

Marei HE ，Althani A ，Afifi N ，Hasan A ，Caceci T ，Pozzoli G ，Cenciarelli C ... -  《Cancer Medicine》

Current Immunotherapies for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.

Huang B ，Li X ，Li Y ，Zhang J ，Zong Z ，Zhang H ... -  《Frontiers in Immunology》

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment.

Glioblastoma multiforme (GBM) is the most frequently occurring primary brain tumor and has a very poor prognosis, with only around 5% of patients surviving for a period of 5 years or more after diagnosis. Despite aggressive multimodal therapy, consisting mostly of a combination of surgery, radiotherapy, and temozolomide chemotherapy, tumors nearly always recur close to the site of resection. For the past 15 years, very little progress has been made with regards to improving patient survival. Although immunotherapy represents an attractive therapy modality due to the promising pre-clinical results observed, many of these potential immunotherapeutic approaches fail during clinical trials, and to date no immunotherapeutic treatments for GBM have been approved. As for many other difficult to treat cancers, GBM combines a lack of immunogenicity with few mutations and a highly immunosuppressive tumor microenvironment (TME). Unfortunately, both tumor and immune cells have been shown to contribute towards this immunosuppressive phenotype. In addition, current therapeutics also exacerbate this immunosuppression which might explain the failure of immunotherapy-based clinical trials in the GBM setting. Understanding how these mechanisms interact with one another, as well as how one can increase the anti-tumor immune response by addressing local immunosuppression will lead to better clinical results for immune-based therapeutics. Improving therapeutic delivery across the blood brain barrier also presents a challenge for immunotherapy and future therapies will need to consider this. This review highlights the immunosuppressive mechanisms employed by GBM cancers and examines potential immunotherapeutic treatments that can overcome these significant immunosuppressive hurdles.

Pearson JRD ，Cuzzubbo S ，McArthur S ，Durrant LG ，Adhikaree J ，Tinsley CJ ，Pockley AG ，McArdle SEB ... -  《Frontiers in Immunology》