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Manuscript Submission Deadline 14 September 2023

Glioma is the most common primary central nervous system cancer in adults, and nearly half of them are WHO Grade IV glioblastoma (GBM), the most malignant form. Recent studies have shown that GBM has surpassed liver and pancreatic cancer as the most difficult cancer to treat, with a 5-year survival rate of ...

Glioma is the most common primary central nervous system cancer in adults, and nearly half of them are WHO Grade IV glioblastoma (GBM), the most malignant form. Recent studies have shown that GBM has surpassed liver and pancreatic cancer as the most difficult cancer to treat, with a 5-year survival rate of 5.5%. Currently, the conventional therapies for GBM include surgical resection, radiotherapy, and chemotherapy (temozolomide), but the survival outcomes of GBM patients have not improved significantly. Immunotherapy has brought hope to cancer treatment, revolutionizing the prognosis of many patients with advanced solid tumors, such as melanoma, non-small cell lung cancer, and renal cell carcinoma. Unfortunately, current immunotherapies have shown little success in treating adult GBM.

Multiple studies have shown that GBM is a highly immunosuppressive tumor. Although myeloid cells may be a key factor in GBM immunosuppression, the exact mechanism of immune escape is still unknown. The proportion of infiltrating tumor-associated microglia and macrophages (TAMs) in GBM far exceeds that of infiltrating T cells. The main TAMs in GBM present as M2-like phenotype, which highly express and secrete cytokines, such as TGFβ and IL-10, forming and maintaining the immunosuppressive microenvironment in GBM. Besides, Tregs also play an important role in the immunosuppressive microenvironment in GBM. On the one hand, Tregs inhibit the activation of effector T cells through the combination of CTLA-4 and CD80/86. On the other hand, Tregs secrete immunosuppressive cytokines, such as IDO and TGFβ, to inhibit the activation of dendritic cells (DC) and other lymphocytes, thus promoting GBM immunosuppression. Based on the gradual understanding of GBM immunosuppression, novel immunotherapy strategies have been developed, including cancer vaccines, oncolytic viruses, chimeric antigen receptor T (CAR-T) cell therapy, cytokine treatment, DC therapy, nanomedicine-mediated immunotherapy, and immune checkpoint blockade, etc.

In this Research Topic, we welcome original research and review articles related to the mechanism of immunosuppression and novel immunotherapy strategies for GBM. Data from both clinical and basic studies are welcome for submissions. Potential topics include, but are not limited to:
1. Molecular mechanism of immunosuppression by glioblastoma.
2. Cellular basis of immune microenvironment of glioblastoma.
3. Novel immunotherapies for glioblastoma with enhanced efficacy, including new drug targets, adoptive cell therapy, (mRNA) cancer vaccines, oncolytic viruses, immune checkpoint inhibitors, and so on.
4. Nanomedicines for glioblastoma immunotherapy: new nanomedicines are designed to cross the blood-brain barrier, target the glioblastoma, elicit immunogenic cell death, rescue immunosuppressive microenvironment, and recruit immune cells, thereby synergizing with immunotherapy.
5. Biomarkers that can be identified as prognostic indicators for immunotherapy.
6. Crosstalk between immunosuppression and apoptosis/ pyroptosis/necrosis/neuroinflammation/oxidative stress.

Keywords: glioblastoma, immunotherapy, immune microenvironment, metastasis, molecular mechanism, neuroinflammation, immunosuppression, nanomedicine


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