History and current state of immunotherapy in glioma and brain metastasis

McGranahan, Tresa; Li, Gordon; Nagpal, Seema

doi:10.1177/1758834017693750

Cited by 59 publications

(54 citation statements)

References 162 publications

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“…The aggressive and invasive characteristics lead to the high recurrence rate and poor prognosis of GBM. Although combined treatments, including surgical resection, radiotherapy, chemotherapy, and immunotherapy, achieve a measure of progress, the late‐stage outcomes of GBM are not encouraging due to high metastasis and invasiveness . Therefore, seeking out new molecules correlated to GMB progression is of extreme urgency.…”

Section: Introductionmentioning

confidence: 99%

AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

Ren

2019

Cancer Science

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Long non‐coding RNAs (lncRNAs) are crucial regulators in various malignancies including glioblastoma multiforme (GBM). In the present study, we screened out a new lncRNA, AC016405.3, through a previous genome‐wide lncRNA microarray analysis in GBM. It showed that AC016405.3 was downregulated in GBM tissue specimens and cell lines, and it also illustrated that the downregulated AC016405.3 was closely correlated with several aggressive features of patients with GBM. Functionally, we found that overexpression of AC016405.3 suppressed GBM cells’ proliferation and metastasis using a gain of function experiment. We further showed that microRNA (miR)‐19a‐5p, a carcinogenic miRNA, was a downstream miRNA of AC016405.3. AC016405.3 was revealed as a target of miR‐19a‐5p, and overexpression of miR‐19a‐5p reversed the inhibitive effect of AC016405.3 on GBM cell proliferation and metastasis. Furthermore, a novel downstream gene of miR‐19a‐5p, TET2 , was identified through a constructed microarray analysis. We showed that TET2 was downregulated in GBM and was involved in miR‐19a‐5p‐mediated proliferation and metastasis by directly being targeted. Finally, through a western blot assay and a series of functional CCK‐8 and metastatic assays, we showed that AC016405.3 suppressed proliferation and metastasis through modulation of TET2 by sponging of miR‐19a‐5p in GBM cells. In summary, the findings of the current study identified a novel lncRNA and illustrated that AC016405.3, acting as an anti‐oncogene, suppressed GBM cell proliferation and metastasis by regulating TET through miR‐19a‐5p sponging. Our present study might provide a new axis in the molecular treatment of GBM.

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Section: Introductionmentioning

confidence: 99%

AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

Ren

2019

Cancer Science

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“…In addition, tumor microenvironment cytokines recruit TANs and immunosuppressive regulatory T cells to the tumor microenvironment, which results in aggressive tumor growth and development of treatment resistance in many cancers, including glioma [27,57]. Mutant IDH1 glioma tumors, which are less aggressive than wild-type IDH1 tumors, have low TAN infiltration [21].…”

Section: Tans In Glioma Progressionmentioning

confidence: 99%

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Khan

Mittal

McGee

et al. 2020

IJMS

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Recent efforts in brain tumor research have been directed towards the modulation of the immune system for therapeutic interventions. Several human cancers, including gliomas, are infiltrated with immune cell types—including neutrophils and myeloid-derived suppressor cells—that contribute to tumor progression, invasiveness, and treatment resistance. The role of tumor-associated neutrophils and myeloid-derived suppressor cells in cancer biology remains elusive, as these cells can exert a multitude of pro-tumor and antitumor effects. In this review, we provide the current understanding and novel insights on the role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance, as well as the mechanisms of pleiotropic behaviors in these cells during disease progression, with an emphasis on possible strategies to reprogram these cells towards their antitumor actions.

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“…Figure 1B, the mean expression of ICR genes, or ICR score, varies between cancer types, reflecting general differences in tumor immunogenicity between cancers. While brain tumors (brain lower grade glioma's (LGG) and glioblastoma multiforme (GBM)) typically display low immune activity (McGranahan et al, 2017), skin cutaneous melanoma (SKCM) and head and neck squamous cell carcinoma (HNSC) display high levels of immune activation (Economopoulou et al, 2016;Passarelli et al, 2017). In addition, the distribution of ICR scores among patients and the difference between the highest and lowest ICR scores varies between cancers.…”

Section: Prognostic Impact Of Icr Classification Is Different Betweenmentioning

confidence: 99%

Conditional activation of immune-related signatures and prognostic significance: a pan-cancer analysis

Roelands

Hendrickx

Kuppen

et al. 2019

Preprint

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43An immune active cancer phenotype typified by a T helper 1 (Th-1) immune response has 44 been associated with increased responsiveness to immunotherapy and favorable prognosis 45 in some but not all cancer types. The reason of this differential prognostic connotation remains 46 unknown. Through a multi-modal Pan-cancer analysis among 31 different histologies (9,282 47 patients), we demonstrated that the favorable prognostic connotation conferred by the 48 presence of a Th-1 immune response was abolished in tumors displaying specific tumor-cell 49 intrinsic attributes such as high TGF-ß signaling and low proliferation capacity. This 50 observation was validated in the context of immune-checkpoint inhibition. WNT-ß catenin, 51 barrier molecules, Notch, hedgehog, mismatch repair, telomerase activity, and AMPK 52 signaling were the pathways most coherently associated with an immune silent phenotype 53 together with mutations of driver genes including IDH1/2, FOXA2, HDAC3, PSIP1, MAP3K1, 54 KRAS, NRAS, EGFR, FGFR3, WNT5A, and IRF7. Our findings could be used to prioritize 55 hierarchically relevant targets for combination therapies and to refine stratification algorithms. 56 57 Keywords 58 -Pan-cancer 59 -Immunologic Constant of Rejection 60 -Prognosis 61 -Mutational load 62 -Neoantigen load 63 -Aneuploidy 64 -Tumor intrinsic pathway enrichment 65 -Cancer Immunotherapy phenotypes (Hendrickx et al., 2017). In particular, we reported that transcriptional 104 dysregulation of the MAPK pathways sustained by genetic alterations (i.e., MAP3K1 and 105 MAP2K4 mutations) are enriched in immune silent tumors (Hendrickx et al., 2017). We also 106 observed that the ICR signature refines and improves the prognostic value of conventional 107 prognostic signatures adopted in breast cancer (Bertucci et al., 2018). Here, we propose a 108 systematic analysis of the entire TCGA cohort encompassing 31 different histologies. Using a 109 pan-cancer approach, we identified novel relationships between tumor genetic programs and 110 immune orientation. After having demonstrated differential associations between ICR 111 classification and overall survival across cancer types, we systemically analyzed in which 112 (molecular) contexts ICR has prognostic value and in which ones it does not. Combination of 113 immune orientation with tumor intrinsic attributes that interact with its prognostic significance 114 could refine tumor immunologic classifications. This approach was validated in the context of 115 immune-checkpoint inhibition allowing better predictive precision.

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History and current state of immunotherapy in glioma and brain metastasis

Cited by 59 publications

References 162 publications

AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Conditional activation of immune-related signatures and prognostic significance: a pan-cancer analysis

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