Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies

Genoud, Vassilis; Migliorini, Denis

doi:10.3390/ijms22073493

Cited by 6 publications

(8 citation statements)

References 129 publications

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“…At present, the standard of care (SOC) management of GBM is based on the maximum safe surgical removal, radiotherapy, and chemotherapy with temozolomide. However, patients with GBM still have a poor prognosis, and SOC will lead to irreversible toxicity, such as neurological deficits due to surgery, neurocognitive impairments with radiotherapy, and systemic toxicity ( 80 , 81 ). It has been confirmed that immunotherapy is highly effective in inhibiting cancer regression and improving patient quality of life ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Immune landscape-based machine-learning–assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma

et al. 2022

Front. Immunol.

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IntroductionAs a malignant brain tumor, glioblastoma (GBM) is characterized by intratumor heterogeneity, a worse prognosis, and highly invasive, lethal, and refractory natures. Immunotherapy has been becoming a promising strategy to treat diverse cancers. It has been known that there are highly heterogeneous immunosuppressive microenvironments among different GBM molecular subtypes that mainly include classical (CL), mesenchymal (MES), and proneural (PN), respectively. Therefore, an in-depth understanding of immune landscapes among them is essential for identifying novel immune markers of GBM.Methods and resultsIn the present study, based on collecting the largest number of 109 immune signatures, we aim to achieve a precise diagnosis, prognosis, and immunotherapy prediction for GBM by performing a comprehensive immunogenomic analysis. Firstly, machine-learning (ML) methods were proposed to evaluate the diagnostic values of these immune signatures, and the optimal classifier was constructed for accurate recognition of three GBM subtypes with robust and promising performance. The prognostic values of these signatures were then confirmed, and a risk score was established to divide all GBM patients into high-, medium-, and low-risk groups with a high predictive accuracy for overall survival (OS). Therefore, complete differential analysis across GBM subtypes was performed in terms of the immune characteristics along with clinicopathological and molecular features, which indicates that MES shows much higher immune heterogeneity compared to CL and PN but has significantly better immunotherapy responses, although MES patients may have an immunosuppressive microenvironment and be more proinflammatory and invasive. Finally, the MES subtype is proved to be more sensitive to 17-AAG, docetaxel, and erlotinib using drug sensitivity analysis and three compounds of AS-703026, PD-0325901, and MEK1-2-inhibitor might be potential therapeutic agents.ConclusionOverall, the findings of this research could help enhance our understanding of the tumor immune microenvironment and provide new insights for improving the prognosis and immunotherapy of GBM patients.

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Section: Discussionmentioning

confidence: 99%

Immune landscape-based machine-learning–assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma

et al. 2022

Front. Immunol.

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“…Therefore, formulating a standardized DC preparation process will be conducive to produce a better treatment effect. 103 T A B L E 1 Clinical trials of glioma DC vaccines from the perspective of cultured mature DC DTH: Delayed type hypersensitivity; GAA: Glioma associate antigen; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFN-α: Interferon-α; IFN-γ: Interferon-γ; IL-4: Interleukin-4; IL-6: Interleukin-6; IL-1β: Interleukin-1β; OS: Overall Survival; PFS: Progression-free survival; PGE-2:Prostaglandin E2; poly-IC: Polyinosinic-Polycytidylic acid; TNF-α: Tumor necrosis factor-α; TTP: Time to progression. ICT-107 ↑ : DC pulsed with MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2…”

Section: Challenge and Methods 1: Standardizing DC Maturation Methodsmentioning

confidence: 99%

“…Therefore, formulating a standardized DC preparation process will be conducive to produce a better treatment effect. 103 …”

Section: Existing Challenges and Future Approaches To DC Immunotherapymentioning

confidence: 99%

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Zhou

Jia

et al. 2022

Cancer Medicine

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Introduction Gliomas, especially the glioblastomas, are one of the most aggressive intracranial tumors with poor prognosis. This might be explained by the heterogeneity of tumor cells and the inhibitory immunological microenvironment. Dendritic cells (DCs), as the most potent in vivo functional antigen‐presenting cells, link innate immunity with adaptive immunity. However, their function is suppressed in gliomas. Therefore, overcoming the dysfunction of DCs in the TME might be critical to treat gliomas. Method In this paper we proposed the specificity of the glioma microenvironment, analyzed the pathways leading to the dysfunction of DCs in tumor microenvironment of patients with glioma, summarized influence of DC‐based immunotherapy on the tumor microenvironment and proposed new development directions and possible challenges of DC vaccines. Result DC vaccines can improve the immunosuppressive microenvironment of glioma patients. It will bring good treatment prospects to patients. We also proposed new development directions and possible challenges of DC vaccines, thus providing an integrated understanding of efficacy on DC vaccines for glioma treatment.

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“…Two reviews in the Special Issue are addressed to the analysis of current molecular targeting strategies in gliomas. In detail, Genoud and Migliorini focused their attention on immunotherapeutic approaches in glioblastoma [ 6 ]. Glioblastomas, the high-grade gliomas, are the most frequent and aggressive primary tumors of the central nervous system in adults, and no clear improvements over current the standard of care have been made in the last decade.…”

mentioning

confidence: 99%

“…Differently from other neoplasms and brain metastasis, immunotherapy has still not proven its efficacy in gliomas. Genaud and Migliorini reviewed the key glioblastoma immune-related features and the current immunotherapeutic strategies explored with their caveats [ 6 ]. Typical hallmarks of gliomas are molecular alterations of the RTK/PI3K/mTOR axis, and its targeting still represents a strong rationale for developing therapeutic strategies against gliomas.…”

mentioning

confidence: 99%

Special Issue “Tumors of the Nervous System: New Insights into Signaling, Genetics and Therapeutic Targeting”

Bartolomeo

Segatto

2022

IJMS

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Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies

Cited by 6 publications

References 129 publications

Immune landscape-based machine-learning–assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma

Immune landscape-based machine-learning–assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Special Issue “Tumors of the Nervous System: New Insights into Signaling, Genetics and Therapeutic Targeting”

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