Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial

Yu, Yao; Luo, Fengming; Tang, Chao; Chen, Dikang; Qin, Zhiyong; Hua, Wei; Xu, Ming; Zhong, Ping; Yu, Shuangquan; Chen, Di; Ding, Xiaojie; Zhang, Yi; Xiao, Zheng; Jiao, Yang; Qian, Jiawen; Deng, Yuting; Hoon, Dave S. B.; Hu, Jian; Chu, Yiwei; Zhou, Lei

doi:10.1007/s00262-018-2232-y

Cited by 72 publications

(57 citation statements)

References 28 publications

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“…PD‐1/PD‐L1 expression was also one of the most important impediments for the efficacy of DC vaccines in cancer immunotherapy. Consistently, it is demonstrated that PD‐L1 expression levels can predict the response to treatment with the DC vaccine in patients with glioblastoma . Several investigators have tried to block PD‐L1 in DCs or PD‐1 in T cells to increase the efficacy of anti‐cancer DC vaccines.…”

Section: Discussionmentioning

confidence: 81%

“…Consistently, it is demonstrated that PD-L1 expression levels can predict the response to treatment with the DC vaccine in patients with glioblastoma. 28 Several investigators have tried to block PD-L1 in DCs or PD-1 in T cells to increase the efficacy of anti-cancer DC vaccines. However, none of them has investigated the impact of concomitant suppression of both PD-1 and PD-L1 at the same time.…”

Section: Discussionmentioning

confidence: 99%

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Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

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Summary Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

et al. 2019

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“…Previously, Yao et al ( 30 ) showed that VTCN1 has a crucial role in the creation and maintenance of the immunosuppressive microenvironment in gliomas, correlating with prognosis and malignant grades. Furthermore, lower levels of VTCN1 are associated with a higher survival in a clinical trial of DC based vaccination ( 31 ). This is in contrast with our observations, which appears to show a protective role for VTCN1 in GBM.…”

Section: Discussionmentioning

confidence: 99%

Profiling of inhibitory immune checkpoints in glioblastoma: Potential pathogenetic players

et al. 2020

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Glioblastoma (GBM) represents the most frequent glial tumor, with almost 3 new cases per 100,000 people per year. Despite treatment, the prognosis for GBM patients remains extremely poor, with a median survival of 14.6 months, and a 5-year survival less than 5%. It is generally believed that GBM creates a highly immunosuppressive microenvironment, sustained by the expression of immune-regulatory factors, including inhibitory immune checkpoints, on both infiltrating cells and tumor cells. However, the trials assessing the efficacy of current immune checkpoint inhibitors in GBM are still disappointing. In the present study, the expression levels of several inhibitory immune checkpoints in GBM (CD276, VTCN1, CD47, PVR, TNFRSF14, CD200, LGALS9, NECTIN2 and CD48) were characterized in order to evaluate their potential as prognostic and eventually, therapeutic targets. Among the investigated immune checkpoints, TNFRSF14 and NECTIN2 were identified as the most promising targets in GBM. In particular, a higher TNFRSF14 expression was associated with worse overall survival and disease-free survival, and with a lower Th1 response.

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“…Moreover, researchers have been made efforts to accelerate precision medicine. Yao 2018 et al found IDH WT TERT MT has better efficacy in GBM IMCT group [16]. Annick 2018 et al confirmed that the mutation of IDH R132 in GBM IMCT group has survival advantage [17].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immunotherapy and Standard of Care in High-Grade Gliomas: A Systematic Review and Meta-analysis

Zhang¹,

Xu²,

Chen³

et al. 2019

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BACKGROUND: While immunotherapy combined with standard of care (SOC) is often used for high-grade glioma (HGG), there have been few comparisons between immunotherapy combined SOC treatment (IMCT) and SOC alone. For clinicians seeking to increase immunotherapies’ efficacy, it is important to understand what interventions exist and their relative effectiveness. METHODS: The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion. Subgroup analysis and Cox proportional hazards modeling was used to examine factors associated with overall survival (OS). Progression-free survival (PFS), objective response rate (ORR), and occurrence rate of adverse events (AE) were included as secondary endpoints to further assess the efficacy and safety of IMCT. GRADE profiler was applied to assess the quality of evidence. This study is registered with PROSPERO, number CRD42019112356 RESULTS: The search yielded 2315 results of which 13 met eligibility criteria. We identified 13 publications, 14 randomized controlled trials (RCTs), and 5 historical-matched controlled trials(HMCTs). In a fixed effects model, Compared to SOC alone, IMCT improved OS (HR = 0.82; 95% CI 0.74-0.90; p < 0.0001), PFS (HR = 0.61; 95% CI 0.40-0.92; p = 0.019), ORR (RR = 2.13; 95% CI 2.56-2.92; p < 0.0001) bur increased the occurrence rate of AE (p < 0.0001). CONCLUSIONS: It suggests that IMCT compared to SOC alone have considerable effectiveness. Our findings support the use of immunotherapy in brain tumor to improve HGG outcomes.

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Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial

Cited by 72 publications

References 28 publications

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Blockage of immune checkpoint molecules increases T‐cell priming potential of dendritic cell vaccine

Profiling of inhibitory immune checkpoints in glioblastoma: Potential pathogenetic players

Efficacy and Safety of Immunotherapy and Standard of Care in High-Grade Gliomas: A Systematic Review and Meta-analysis

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