Immunological Aspects of Malignant Gliomas

Cohen-Inbar, Or; Zaaroor, Menashe

doi:10.1017/cjn.2016.34

Cited by 13 publications

(13 citation statements)

References 85 publications

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Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

“…*based on Cohen-Inbar et al [1] less valid with respect to its prognostic significance serving as somewhat of a wastebasket category. Multiple molecular subsets of GBM are now known, carrying different prognostic horizons [1] . Despite standard of care treatment, the median survival of a patient harboring a GBM is less than 2 years, a grim figure which changed very little in the past decades, proving resistant to most developments and revolutions incurred on modern medicine [2][3][4] .…”

Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

“…Early reports of GBM patients who endured a post-operative surgical-site infection who surprisingly exhibited longer survival sparked an interest in many clinicians, suspecting an important role for the immune system both in disease progression as well as in tumor triumph. Since these initial pivotal observations, with developing techniques and widespread interest, multiple studies were put forward describing different molecular immunosuppressive mechanisms taking place in GBM cells and microenvironment, claiming these to be the dominant key events (table 1) [1,5] . Unfortunately, things are not as straightforward or simple, and both arms of the immune system are known to be hampered in GBM, as do many other anatomical barriers, micro-environmental conditions and features unique to tumors within the central nervous system, once termed as immune-privileged [27][28] .…”

Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

“…macrophages), ƜCytotoxic (CD8+) T-lymphocytes, ƩSquamous Cell Carcinoma, ϦTumor infiltrating lymphocytes. + Based on Cohen-Inbar et al [5] developed mechanisms to evade or block its development at multiple steps (Table 1) [1,5] . Tumor associated target antigens must be sufficiently different from self-antigens, avoiding the development of immune-tolerance and anergy to self (and consequently to the tumor) on the one hand or the development of an auto-immune response on the other.…”

Section: Gbm Mediated Immune-evasionmentioning

confidence: 99%

“…A local inflammatory response should than be instigated and properly regulated. The multitude of immunosuppressive mechanisms (both active and passive) as well as immune-evasion techniques attributed to GBM cells are summarized in Table 1 [1,5] . These mechanisms independently, support the evolution of anergy and tolerance to the tumor.…”

Section: Gbm Mediated Immune-evasionmentioning

confidence: 99%

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Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

Cohen-Inbar¹

2016

Inflamm Cell Signal

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Glioblastoma Multiforme (GBM, Astrocytoma grade-IV) is the most common primary malignant brain tumour in adults and unfortunately the most deadly. Patients with GBM exhibit a deficient anti-tumor immune response. Immunotherapy is rapidly becoming one of the pillars of anti-cancer therapy. GBM has not received similar clinical successes as of yet, a fact which may be attributed to its relative inaccessibility, its poor immunogenicity, or any of the many other immune mechanisms known to be inactivated in these tumor cells. Focused Ultrasound (FUS) is emerging as a promising treatment approach. The effects of FUS on the tissue are not merely thermal. Reported FUS-induced acoustic cavitation which carries both mechanical and molecular implications as well as FUS induced immunomodulation play important roles. This is a concise research highlights on a comprehensive report by the same group. We separately discuss the different pertinent immunosuppressive mechanisms harnessed by GBM and the immunomodulatory effects of FUS. The three modes of FUS action can all be assigned a molecular final common pathway of immunomodulation. Thermal ablation induced immune effects, microbubbles effects in disrupting the BBB and introducing antigens and drugs to the tumor milieu as well as FUS induced molecular effects are discussed. The effect of FUS on the pro-inflammatory cytokines secretion profile, the stress response, the intra-tumoral immune-cells populations, dendritic cells activity moderation and FUS induced increased cytotoxic cells potency are all discussed. A conceptual synopsis of the synergistic treatment of GBM utilizing FUS and immunotherapy is presented. The interaction of multiple approaches harnessing immune-components and circumventing immunosuppressing mechanisms may herald a new era in the fight against GBM.

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Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

Section: Anti-apoptosis Upregulation Of Anti-apoptotic Proteins (Iementioning

confidence: 99%

Section: Gbm Mediated Immune-evasionmentioning

confidence: 99%

Section: Gbm Mediated Immune-evasionmentioning

confidence: 99%

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Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

Cohen-Inbar¹

2016

Inflamm Cell Signal

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Deep Learning Glioma Grading with the Tumor Microenvironment Analysis Protocol for Comprehensive Learning, Discovering, and Quantifying Microenvironmental Features

Pytlarz,

Wojnicki,

Pilanc

et al. 2024

j Imaging. Inform. med.

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Gliomas are primary brain tumors that arise from neural stem cells, or glial precursors. Diagnosis of glioma is based on histological evaluation of pathological cell features and molecular markers. Gliomas are infiltrated by myeloid cells that accumulate preferentially in malignant tumors, and their abundance inversely correlates with survival, which is of interest for cancer immunotherapies. To avoid time-consuming and laborious manual examination of images, a deep learning approach for automatic multiclass classification of tumor grades was proposed. As an alternative way of investigating characteristics of brain tumor grades, we implemented a protocol for learning, discovering, and quantifying tumor microenvironment elements on our glioma dataset. Using only single-stained biopsies we derived characteristic differentiating tumor microenvironment phenotypic neighborhoods. The study was complicated by the small size of the available human leukocyte antigen stained on glioma tissue microarray dataset — 206 images of 5 classes — as well as imbalanced data distribution. This challenge was addressed by image augmentation for underrepresented classes. In practice, we considered two scenarios, a whole slide supervised learning classification, and an unsupervised cell-to-cell analysis looking for patterns of the microenvironment. In the supervised learning investigation, we evaluated 6 distinct model architectures. Experiments revealed that a DenseNet121 architecture surpasses the baseline’s accuracy by a significant margin of 9% for the test set, achieving a score of 69%, increasing accuracy in discerning challenging WHO grade 2 and 3 cases. All experiments have been carried out in a cross-validation manner. The tumor microenvironment analysis suggested an important role for myeloid cells and their accumulation in the context of characterizing glioma grades. Those promising approaches can be used as an additional diagnostic tool to improve assessment during intraoperative examination or subtyping tissues for treatment selection, potentially easing the workflow of pathologists and oncologists. Graphical Abstract

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Glioblastoma multiforme targeted therapy: The Chlorotoxin story

Cohen-Inbar

Zaaroor

2016

Journal of Clinical Neuroscience

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Immunological Aspects of Malignant Gliomas

Cited by 13 publications

References 85 publications

Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

Deep Learning Glioma Grading with the Tumor Microenvironment Analysis Protocol for Comprehensive Learning, Discovering, and Quantifying Microenvironmental Features

Glioblastoma multiforme targeted therapy: The Chlorotoxin story

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