Glioblastoma Immune Landscape and the Potential of New Immunotherapies

Daubon, Thomas; Hémadou, Audrey; Romero-Garmendia, Irati; Saleh, Maya

doi:10.3389/fimmu.2020.585616

Cited by 82 publications

(66 citation statements)

References 107 publications

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“…Immunotherapy has been shown to be a viable treatment option for advanced or aggressive cancers [ 44 ]. Given that the overall survival of LGG patients treated with immunotherapy is still very low [ 45 ], identifying patients who will benefit the most from these treatments is critical, but we have yet to develop a reliable model for predicting immunotherapy response and overall survival. Our work looked at the relationship between APOBEC3 expression and immunotherapy biomarkers, such as PD-L1, CTLA-4, and LAG-3, and found that the high expression group had significantly higher levels than the low expression group, implying a better response [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

Luo

Wang

Liao³

et al. 2021

IJMS

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Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) has been identified as a group of enzymes that catalyze cytosine deamination in single-stranded (ss) DNA to form uracil, causing somatic mutations in some cancers. We analyzed the APOBEC3 family in 33 TCGA cancer types and the results indicated that APOBEC3s are upregulated in multiple cancers and strongly correlate with prognosis, particularly in low grade glioma (LGG). Then we constructed a prognostic model based on family expression in LGG where the APOBEC3 family signature is an accurate predictive model (AUC of 0.85). Gene mutation, copy number variation (CNV), and a differential gene expression (DEG) analysis were performed in different risk groups, and the weighted gene co-expression network analysis (WGCNA) was employed to clarify the role of various members in LGG; CIBERSORT algorithm was deployed to evaluate the landscape of LGG immune infiltration. We found that upregulation of the APOBEC3 family expression can strengthen Ras/MAPK signaling pathway, promote tumor progression, and ultimately reduce the treatment benefits of Raf inhibitors. Moreover, the APOBEC3 family was shown to enhance the immune response mediated by myeloid cells and interferon gamma, as well as PD-L1 and PD-L2 expression, implying that they have immunotherapy potential. Therefore, the APOBEC3 signature enables an efficient assessment of LGG patient survival outcomes and expansion of clinical benefits by selecting appropriate individualized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

Luo

Wang

Liao³

et al. 2021

IJMS

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“…However, this strategy does not bypass the issue of expression of MHC I molecules on glioblastoma cells and the subsequent inhibition of NK cells. Yet, such a combined treatment induces NK cells to create a pro-inflammatory environment and improves the survival rate of glioblastoma patients [ 83 ] by recruiting immune cells [ 84 ].…”

Section: Nk Cells As a Possible Immunotherapy Approach To Treat Glmentioning

confidence: 99%

Regulation of MHC I Molecules in Glioblastoma Cells and the Sensitizing of NK Cells

et al. 2021

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Immunotherapy has been established as an important area in the therapy of malignant diseases. Immunogenicity sufficient for immune recognition and subsequent elimination can be bypassed by tumors through altered and/or reduced expression levels of major histocompatibility complex class I (MHC I) molecules. Natural killer (NK) cells can eliminate tumor cells in a MHC I antigen presentation-independent manner by an array of activating and inhibitory receptors, which are promising candidates for immunotherapy. Here we summarize the latest findings in recognizing and regulating MHC I molecules that affect NK cell surveillance of glioblastoma cells.

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“…Clinical activity of PD-1/PD-L1 blockade seems not to be significantly increased by the addition of antiangiogenic therapy [ 36 , 37 , 38 , 39 ], and the same consideration currently has to be made for dual immune checkpoint blockade. However, a new wave of novel and promising combinatorial strategies of ICIs with different modalities such as oncolytic viruses, vaccines, chimeric antigen receptor (CAR) T cells have begun their clinical development [ 70 ], with the hope of effectively boost antitumor immunity and bringing to the clinic effective therapeutic options for HGG patients.…”

Section: Future Perspectivesmentioning

confidence: 99%

Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives

Persico

Lorenzi

Dipasquale

et al. 2021

JCM

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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in many advanced malignancies. Unfortunately, these clinical successes have not been replicated in the neuro-oncology field so far. This review summarizes the status of ICI investigation in high-grade gliomas, critically presenting the available data from preclinical models and clinical trials. Moreover, we explore new approaches to increase ICI efficacy, with a particular focus on combinatorial strategies, and the potential biomarkers to identify patients most likely to benefit from immune checkpoint blockade.

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Glioblastoma Immune Landscape and the Potential of New Immunotherapies

Cited by 82 publications

References 107 publications

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma

Regulation of MHC I Molecules in Glioblastoma Cells and the Sensitizing of NK Cells

Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives

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