Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas

Grady, Clare; Melnick, Kaitlyn; Porche, Ken; Dastmalchi, Farhad; Hoh, Daniel J.; Rahman, Maryam; Ghiaseddin, Ashley

doi:10.14245/ns.2143210.605

Cited by 18 publications

(20 citation statements)

References 106 publications

(356 reference statements)

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“…However, the previous study reported that gross-total resection followed by radiotherapy had beneficial effects on the overall outcome of PSC GB in the pediatric age group[ 23 , 24 ]. More effective and targeted therapies need specific investigation in the future for helping patients with unique gene mutations achieve better prognosis[ 25 , 26 ]. Further, broadening treatment avenues would help improve the efficacy of therapies and help in recovery for these patients.…”

Section: Discussionmentioning

confidence: 99%

Atypical imaging features of the primary spinal cord glioblastoma: A case report

Li¹,

Chen²,

Li³

et al. 2022

WJCC

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BACKGROUND Primary spinal cord (PSC) glioblastoma (GB) is an extremely rare but fatal primary tumor of the central nervous system and associated with a poor prognosis. While typical tumor imaging features are generally easy to recognize, glioblastoma multiforme can have a wide range of imaging findings. Atypical GB is often misdiagnosed, which usually delays the optimal time for treatment. In this article, we discuss a clinical case of pathologically confirmed PSC GB under the guise of benign tumor imaging findings, as well as the most recent literature pertaining to PSC GB. CASE SUMMARY A 70-year-old female complained of limb weakness lasting more than 20 d. Irregular masses were observed inside and outside the left foramina of the spinal canal at C7-T1 on medical imaging. Based on the imaging features, radiologists diagnosed the patient with schwannoma. Tumor resection was performed under general anesthesia. The final histopathological findings revealed a final diagnosis of PSC GB, world health organization Grade IV. The patient subsequently underwent a 4-wk course of radiotherapy (60 Gy in 20 fractions) combined with temozolomide chemotherapy. The patient was alive at the time of submission of this manuscript. CONCLUSION Atypical GB presented unusual imaging findings, which led to misdiagnosis. Therefore, a complete recognition of imaging signs may facilitate early accurate diagnosis.

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Section: Discussionmentioning

confidence: 99%

Atypical imaging features of the primary spinal cord glioblastoma: A case report

Li¹,

Chen²,

Li³

et al. 2022

WJCC

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Section: Clinical Challenges In Treating Gbmmentioning

confidence: 99%

“…The BBB and relative immunologic privilege of the brain are doubtless factors in GBM ranking among the immunologically cold cancer types [ 15 ]. Clinical trials of various immunotherapeutic strategies in patients with GBM have generally shown poor efficacy, despite some signs of inducing some level of immune response against the GBM [ 16 ]. The immune system has some access and communication with the central nervous system (CNS) via glymphatic flow and lymphatics in the meninges [ 17 ], but in general it is somewhat compromised relative to that elsewhere.…”

Section: Clinical Challenges In Treating Gbmmentioning

confidence: 99%

Delivering Glioblastoma a Kick—DGKα Inhibition as a Promising Therapeutic Strategy for GBM

Purow

2022

Cancers

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Diacylglycerol kinase α (DGKα) inhibition may be particularly relevant for the treatment of glioblastoma (GBM), a relatively common brain malignancy incurable with current therapies. Prior reports have shown that DGKα inhibition has multiple direct activities against GBM cells, including suppressing the oncogenic pathways mTOR and HIF-1α. It also inhibits pathways associated with the normally treatment-resistant mesenchymal phenotype, yielding preferential activity against mesenchymal GBM; this suggests possible utility in combining DGKα inhibition with radiation and other therapies for which the mesenchymal phenotype promotes resistance. The potential for DGKα inhibition to block or reverse T cell anergy also suggests the potential of DGKα inhibition to boost immunotherapy against GBM, which is generally considered an immunologically “cold” tumor. A recent report indicates that DGKα deficiency increases responsiveness of macrophages, indicating that DGKα inhibition could also have the potential to boost macrophage and microglia activity against GBM—which could be a particularly promising approach given the heavy infiltration of these cells in GBM. DGKα inhibition may therefore offer a promising multi-pronged attack on GBM, with multiple direct anti-GBM activities and also the ability to boost both adaptive and innate immune responses against GBM. However, both the direct and indirect benefits of DGKα inhibition for GBM will likely require combinations with other therapies to achieve meaningful efficacy. Furthermore, GBM offers other challenges for the application of DGKα inhibitors, including decreased accessibility from the blood-brain barrier (BBB). The ideal DGKα inhibitor for GBM will combine potency, specificity, and BBB penetrability. No existing inhibitor is known to meet all these criteria, but the strong potential of DGKα inhibition against this lethal brain cancer should help drive development and testing of agents to bring this promising strategy to the clinic for patients with GBM.

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“…Glioma is the most common primary intracranial tumor, and it is derived from neuroepithelium and accounts for 50%–60% of brain tumors ( Grady et al, 2022 ; O'Connor et al, 2021 ). At present, the clinical treatment of glioma mainly includes neurosurgical resection, radiotherapy, chemotherapy, and immunotherapy ( Grady et al, 2022 ). Nevertheless, patients have a mere median survival of 14 months, as well as a 5-year survival rate less than 10% ( Birk et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

Xue

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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Glioma is the most common malignant intracranial tumor with low 5-year survival rate. In this study, we constructed a plasmid expressing anti-HAAH single-chain antibody and sTRAIL fusion protein (scFv-sTRAIL), and explored the effects of the double gene modified human umbilical cord mesenchyreal stem cells (hucMSCs) on the growth of glioma in vitro and in vivo. The isolated hucMSCs were identified by detecting the adipogenic differentiation ability and the osteogenic differentiation ability. The phenotypes of hucMSCs were determined by the flow cytometry. The hucMSCs were infected with lentivirus expression scFv-sTRAIL fusion protein. The expression of sTRAIL in hucMSCs were detected by immunofluorescence staining, western blot and ELISA. The tropism of hucMSCs toward U87G cells was assessed by transwell assay. The inhibitory effect of hucMSCs on U87G cells were explored by CCK8 and apoptosis assay. The xenograft tumor was established by subcutaneously injection of U87G cells into the back of mice. The hucMSCs were injected via tail veins. The inhibitory effect of hucMSCs on glioma in vivo was assessed by TUNEL assay. The hucMSCs migrated into the xenograft tumor were revealed by detecting the green fluorescent. The results showed that the scFv-sTRAIL expression did not affect the phenotypes of hucMSCs. The scFv-sTRAIL expression promoted the tropism of hucMSCs toward U87G cells, enhanced the inhibitory effect and tumor killing effect of hucMSCs on U87G cells. The in vivo study showed that hucMSCs expressing scFv-sTRAIL demonstrated significantly higher inhibitory effect and tumor killing effect than hucMSCs expressing sTRAIL. The green fluorescence intensity in the mice injected with hucMSCs expressing scFv-sTRAIL was significantly higher than that injected with hucMSCs expressing sTRAIL. These data suggested that the scFv conferred the targeting effect of hucMSCs tropism towards the xenograft tumor. In conclusion, the hucMSCs expressing scFv-sTRAIL fusion protein gained the capability to target and kill gliomas cells in vitro and in vivo. These findings shed light on a potential therapy for glioma treatment.

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Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas

Cited by 18 publications

References 106 publications

Atypical imaging features of the primary spinal cord glioblastoma: A case report

Atypical imaging features of the primary spinal cord glioblastoma: A case report

Delivering Glioblastoma a Kick—DGKα Inhibition as a Promising Therapeutic Strategy for GBM

The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

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