Current State of Immunotherapy for Treatment of Glioblastoma

McGranahan, Tresa; Therkelsen, Kate E.; Ahmad, Sarah; Nagpal, Seema

doi:10.1007/s11864-019-0619-4

Cited by 253 publications

(217 citation statements)

References 73 publications

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“…Indeed, the landscape of clinical trials exploring combination treatment regimens coupling checkpoint blockade with other therapies is rapidly expanding. [53][54][55][56][57] Quantifying the molecular consequences of these combination regimes with our platform could provide novel insights into these trials and enable the informed design of new therapeutic combinations, potentially with targeted immunotherapies. Taken together, our relative and absolute quantitative immunopeptidomic data demonstrate the utility of quantitative immunopeptidomics in evaluating the pMHC repertoire response to therapy.…”

Section: Repertoire Changes Induced By Ifn-g Stimulation Are Distinctmentioning

confidence: 99%

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

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Mesfin

Joughin

et al. 2020

Preprint

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Peptides bound to class I major histocompatibility complexes (MHC) play a critical role in immune cell recognition and can trigger an antitumor immune response in cancer. Surface MHC levels can be modulated by anticancer agents, altering immunity. However, understanding the peptide repertoire's response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking robust normalization controls. We describe a novel approach that leverages recombinant heavy isotope-coded peptide MHCs (hipMHCs) and multiplex isotope tagging to quantify peptide repertoire alterations using low sample input.HipMHCs improve quantitative accuracy of peptide repertoire changes by normalizing for variation across analyses and enable absolute quantification using internal calibrants to determine copies per cell of MHC antigens, which can inform immunotherapy design. Applying this platform in melanoma to profile the immunopeptidome response to CDK4/6 inhibition and interferon gamma, known modulators of antigen presentation, we uncovered treatment-specific alterations, connecting the intracellular response to extracellular immune presentation.

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Section: Repertoire Changes Induced By Ifn-g Stimulation Are Distinctmentioning

confidence: 99%

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

Stopfer

Mesfin

Joughin

et al. 2020

Preprint

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“…In addition, because radiation may increase antigen presentation and promote the abscopal effect, several clinical trials (NCT02648633, STERIMGLI -NCT02866747, etc.) are underway to examine the efficacy of checkpoint inhibitors in combination with radiation therapy in recurrent glioblastoma [46]. We expect these trials of combination therapy to show synergistic effects, thereby minimizing the brain radiation dose and reducing adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal changes in inflammasomes, apoptosis, and MEMRI after radiation-induced brain injury in juvenile rats

et al. 2020

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Purpose: The aim of this study was to characterize changes in hippocampal inflammasomes, pyroptosis and apoptosis in juvenile rats after brain irradiation and to assess whether manganese-enhanced magnetic resonance imaging (MEMRI) reflected those changes. Materials and methods: Four-week-old male Sprague-Dawley rats received a whole-brain radiation dose of 15 Gy or 25 Gy. Hippocampal inflammasomes and apoptosis were measured using Western blot analysis at 4 days and 8 weeks after irradiation. MEMRI and magnetic resonance spectroscopy (MRS) were performed at the same time points.Results: Neither the 15 Gy nor 25 Gy group showed changes in the expression of inflammasome proteins absent in melanoma 2 (AIM2), gasdermin-D (GSDMD), nucleotide oligomerization domain-like receptor protein 1 (NLRP1) and NLRP3 at 4 days or 8 weeks after radiation injury (P > 0.05). Furthermore, the expression levels of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 were not significantly different among the groups (P > 0.05). The expression levels of cleaved caspase-1 and -3, indicators of apoptosis, were higher in the irradiation groups than in the control group at 4 days post irradiation, especially for caspase-3 (P < 0.05), but this increase was slightly attenuated at 8 weeks after radiation injury. Four days post irradiation, the MEMRI signal intensity (SI) in the irradiation groups, especially the 25 Gy group, was significantly lower than that in the control group (P < 0.05). Eight weeks after radiation injury, the SI of the 15 Gy group and the 25 Gy group recovered by different degrees, but the SI of the 25 Gy group was still significantly lower than that of the control group (P < 0.05). On day 4 post irradiation, the metabolic ratio of N-acetylaspartate (NAA) to creatine (Cr) in the 15 Gy group and 25 Gy group was significantly lower than that in the control group (P < 0.05). The NAA/Cr ratio in the 15 Gy group recovered to control levels at 8 weeks (P > 0.05), but the NAA/Cr ratio in the 25 Gy group remained significantly lower than that in the control group (P < 0.05).Conclusion: Radiation-induced brain injury is dose-dependently associated with apoptosis but not inflammasomes or pyroptosis, and the change in apoptosis can be detected by MEMRI.

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“…Immune system plays a vital role in the development and progression of tumors [14]. In addition, immunotherapy has revolutionized cancer treatment and has been approved for the treatment of manifold tumors recently [15], which has shed new light on the therapy of LUAD.…”

Section: Discussionmentioning

confidence: 99%

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma

2020

Preprint

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Background Lung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. The aim of this study was to establish an immune-related gene pairs (IRGPs) signature for predicting the prognosis of LUAD patients.Methods We downloaded the gene expression profile and immune-related gene set from TCGA and ImmPort database, respectively, to establish IRGPs. Then, IRGPs subjected to univariate Cox regression analysis, LASSO regression analysis and multivariable Cox regression analysis to screen and develop a IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from GEO was used to validate this signature.Results A IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in TCGA set was 0.867 and 0.870, respectively. Similar result was observed in the AUC of GEO set and Total set (GEO set [1-year: 0.819; 3-years: 0.803]; Total set [1-year: 0.845; 3-years: 0.801]). Survival analysis of three sets demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that risk score was independent prognostic factors.Conclusions We developed a novel IRGPs signature for predicting prognosis of LUAD.

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Current State of Immunotherapy for Treatment of Glioblastoma

Cited by 253 publications

References 73 publications

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

Hippocampal changes in inflammasomes, apoptosis, and MEMRI after radiation-induced brain injury in juvenile rats

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma

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