scholarly journals P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eilam Yeini ◽  
Paula Ofek ◽  
Sabina Pozzi ◽  
Nitzan Albeck ◽  
Dikla Ben-Shushan ◽  
...  
Keyword(s):  
Immune System ◽  
Mouse Models ◽  
Brain Cancer ◽  
Stromal Cells ◽  
Crucial Role ◽  
Poor Prognosis ◽  
Immune Modulation ◽  
Cancer Immunity ◽  
The Brain ◽  
Proliferation And Invasion

AbstractGlioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. However, the reciprocal mechanisms by which GB cells alter microglia/macrophages behavior are not fully understood. We propose that these mechanisms involve adhesion molecules such as the Selectins family. These proteins are involved in immune modulation and cancer immunity. We show that P-selectin mediates microglia-enhanced GB proliferation and invasion by altering microglia/macrophages activation state. We demonstrate these findings by pharmacological and molecular inhibition of P-selectin which leads to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophage function and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.

scholarly journals Therapeutic Immunization against Glioblastoma

2018 ◽  
Vol 19 (9) ◽  
pp. 2540 ◽  
Author(s):  
Virgil Schijns ◽  
Chrystel Pretto ◽  
Anna Strik ◽  
Rianne Gloudemans-Rijkers ◽  
Laurent Deviller ◽  
...  
Keyword(s):  
Immune System ◽  
Brain Cancer ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Normal Brain ◽  
Dismal Prognosis ◽  
Medicinal Treatment ◽  
The Brain

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Subjectivity as a sentient perspective and the role of interoception

2018 ◽  
Author(s):  
Helena De Preester
Keyword(s):  
Crucial Role ◽  
Point Of View ◽  
Basic Form ◽  
Bodily States ◽  
The Brain ◽  
Phenomenological Point

This chapter argues that the most basic form of subjectivity is different from and more fundamental than having a self, and forwards a hypothesis about the origin of subjectivity in terms of interoception. None of those topics are new, and a consensus concerning the homeostatic-interoceptive origin of subjectivity is rapidly growing in the domains of the neurosciences and psychology. This chapter critically explores that growing consensus, and it argues that the idea that the brain topographically represents bodily states is unfit for thinking about the coming about of subjectivity. In the first part, four inherent characteristics of subjectivity are discussed from a philosophical phenomenological point of view. The second part explores whether a model of subjectivity in which interoception maintains its crucial role is possible without relying on topographical representations of the in-depth body, and giving due to the inherent characteristics of subjectivity.

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