Novel Immunotherapeutics for Treatment of Glioblastoma: The Last Decade of Research

Khansur, Emaad; Shah, Ashish H.; Lacy, Kyle; Komotar, Ricardo J.

doi:10.1080/07357907.2018.1479414

Cited by 6 publications

(7 citation statements)

References 48 publications

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“…The conventional belief that the blood-brain barrier offers immune privilege no longer seems accurate, suggesting that immunotherapy could have benefits in CNS cancer [21]. Immunotherapy includes vaccine therapy, checkpoint inhibitors, chimeric antigen tcr, and viral immunotherapy, which can improve prognosis and OS for GBM patients [22]. The immune checkpoint inhibitors have improved survival in treatment-resistant solid tumors, including melanoma, NSCLC, and renal cell carcinoma (RCC) [23].…”

Section: Discussionmentioning

confidence: 99%

Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

Long

Liu

et al. 2020

Aging

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Immune-checkpoint therapy has failed to show significant benefit in glioblastoma (GBM) patients. Immunologic subtypes of GBM are necessary to identify patients who might benefit from immune-checkpoint therapy. This study reviewed 152 GBM samples from The Cancer Genome Atlas (TCGA) and 214 GBM samples from Chinese Glioma Genome Atlas (CGGA). Correlation analysis showed that immune checkpoint genes (ICGs) were mainly positively correlated. The prognostic analysis of the overall survival showed that there was a significant correlation between the overall survival (OS) and the prognosis of ICGs, in which the TNFSF14 gene was a significant adverse prognostic factor. Combined with TMB and neoantigens, we found that TNFSF9 and CD27 were significantly negatively correlated with TMB and neoantigens. The association between adaptive immune pathway genes and ICG expression showed that they were positively correlated with ICGs, indicating that adaptive immune pathway genes have a certain regulatory effect on the expression of ICGs. The analysis of clinical features of the samples showed that the higher the expression of ICGs, the more likely to be correlated with mutant isocitrate dehydrogenase (IDH), while the lower the expression level of IDH, the more likely to be significantly correlated with the primary GBM. Survival analysis showed that low expression of PD-L1, IDO1, or CTLA4 with TNFSF14 in the low expression group had the best prognosis, while high expression of IDO1 or CD274 with TNFSF14 in the high expression group and low expression of CTLA4 with TNFSF14 in the high expression group had the worst prognosis. We conclude that TNFSF14 is a biomarker to identify immunologic subtype and prognosis with other ICGs in GBM and may serve as a potential therapeutic target..

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Section: Discussionmentioning

confidence: 99%

Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

Long

Liu

et al. 2020

Aging

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“…Bloch et al revealed a median overall survival oscillating 42 weeks (42.6 weeks) after HSPPC-96 administration in rGBM patients. Further efforts concerning the design of Phase2 studies have been performed [208]. Clinical trials challenging the effectiveness and safety of HSPPC-96 vaccination evaluate overall survival and progression-free time.…”

Section: Tlr-4 In Glioblastoma Multiforme-clinical Applicationmentioning

confidence: 99%

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

Litak

Grochowski

Litak³

et al. 2020

IJMS

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Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

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“…In DC therapy vaccines, the DCs are isolated from the patient's bloodstream and stimulated ex vivo against tumor-specific antigens. Then, the active DCs are reintroduced into the patient organism expecting the mount of a specific immune response against tumoral components [49,51,55,63]. The application of DC therapy in GB has been studied with two main vaccines at two different randomized clinical trials.…”

Section: Dendritic Cell Therapy (Dc)mentioning

confidence: 99%

“…Promising results have been obtained when standard treatment is combined with the vaccine. However, the final results and subsequent phases are awaited [63,65].…”

Section: Dendritic Cell Therapy (Dc)mentioning

confidence: 99%

“…At first, this therapy was developed for direct destruction of tumoral cells, but it has shown a wider range of potential applications. OV immunologic mechanisms include the release of tumor antigens (DAMPs), inhibition of tumoral immunosuppressive genes, transport of pro-inflammatory agents to tumoral cells, and tumoral microenvironmental disruption, among other factors that favor T-cell infiltration and a more effective immune response against the tumor (Figure 2) [18,49,63,[70][71][72][73].…”

Section: Oncolytic Virus Therapymentioning

confidence: 99%

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Glioblastoma Treatment: State-of-the-Art and Future Perspectives

Camacho

Flores-Vázquez

Moscardini-Martelli

et al. 2022

IJMS

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(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve overall survival, free-progression survival, and life quality in glioblastoma patients. (2) Methods: Our objective is to recap the actual state-of-the-art in glioblastoma treatment, resume the actual research and future perspectives on immunotherapy, as well as the new synthetic molecules and natural compounds that represent potential future therapies at preclinical stages. (3) Conclusions: Despite the great efforts in therapeutic research, glioblastoma management has suffered minimal changes, and the prognosis remains poor. Combined therapeutic strategies and delivery methods, including immunotherapy, synthetic molecules, natural compounds, and glioblastoma stem cell inhibition, may potentiate the standard of care therapy and represent the next step in glioblastoma management research.

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Novel Immunotherapeutics for Treatment of Glioblastoma: The Last Decade of Research

Cited by 6 publications

References 48 publications

Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

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