IDH mutational status and the immune system in gliomas: a tale of two tumors?

Choi, Bryan D.; Curry, William T.

doi:10.21037/tcr.2017.09.37

Cited by 17 publications

(10 citation statements)

References 13 publications

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“…It is well established that IDH-1 MUT and IDH-1 WT gliomas have distinct tumor behavior driven by different oncogenic signals and respond differently to current treatment paradigms. Notably, by comparing the immune responses between IDH-1 MUT and IDH-1 WT patients, some studies have identified a marked reduction in the expression of immune-related genes, including the CD274 (PD-L1 coding gene) gene, in IDH-1 MUT gliomas (25)(26)(27). The results were in line with ours, and downregulated sPD-L1 levels tended to occur in glioma patients with IDH-1 MUT tumors.…”

Section: Discussionsupporting

confidence: 87%

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

et al. 2020

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Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type

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Section: Discussionsupporting

confidence: 87%

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

et al. 2020

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“…It is well established that IDH-1 MUT and IDH-1 WT gliomas have distinct tumor behavior driven by different oncogenic signals and respond differently to current treatment paradigms. Notably, by comparing the immune responses between IDH-1 MUT and IDH-1 WT patients, some studies have been identi ed that a marked reduction in expression of immune related genes, including the CD274 (PD-L1 coding gene) gene, in IDH-1MUT gliomas (21)(22)(23). The results were in line with ours, the downregulated sPD-L1 levels tended to occur in the glioma patients with IDH-1 MUT.…”

Section: Discussionsupporting

confidence: 85%

The Change of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcome

Ding

Wang²,

Zhu

et al. 2020

Preprint

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Abstract Background: It has been proved that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in extracranial malignancies. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) still remains unclear.The purpose of this study is to evaluate the concentration of sPD-L1in the plasma of glioma patients before and after RT, and to explore its relationship with clinical outcomes.Methods: Between October 2017 and September 2018, the glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled and the blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) promoter status and Ki-67 expression were evaluated by immunohistochemistry. The murine models of glioma were used to address whether circulating sPD-L1 molecules are directly targeted by the anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson or Spearman correlation. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method.Results: Sixty glioma patients were included, with the median age 52-year-old. The proportion of grade I, II, III, IV were 6.7%, 23.3%, 28.4% and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grades, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/mL as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline level of sPD-L1 (P = 0.027, 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that increased level of sPD-L1 in IDH-1 mutation patients was higher than that in wide-type ones. Furthermore, the murine models of glioma indicate that sPD-L1 can be blocked by anti-PD-L1 antibody. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of combination with immune checkpoint inhibitors and RT might be promising for glioma, especially for patients with IDH-1 mutation.

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“…Circulating tumor cells are separated from the primary tumor or metastasis and enter the systemic circulation. Approaches for the detection of circulating tumor cells include the use of antibodies for immunohistochemical evaluation and subsequent genetic analysis [162], visual methods for research [73], and evaluation of cell sizes [70]. The mechanism of penetration of circulating brain-derived tumor cells into the bloodstream is not fully understood; however, it is assumed that the glioma tumor cells penetrate into the bloodstream due to great invasiveness, which helps to overcome the BBB or even disrupt the BBB function during tumor development [70,163].…”

Section: Perspective Biomarkersmentioning

confidence: 99%

“…Molecular alterations responsible for glioblastoma carcinogenesis [66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85]. …”

Section: Figurementioning

confidence: 99%

Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics

Silantyev

Falzone

Libra

et al. 2019

Cells

179

139

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Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

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IDH mutational status and the immune system in gliomas: a tale of two tumors?

Cited by 17 publications

References 13 publications

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

The Change of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcome

Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics

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