Abstract:
:Immune checkpoints restrain the immune system following its activation and their inhibition unleashes anti-tumor immune responses. Immune checkpoint inhibitors revolutionized the treatment of several cancer types, including melanoma, and immune checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies is becoming a frontline therapy in metastatic melanoma. Notably, up to 60% of metastatic melanoma patients develop metastases in the brain. Brain metastases (BrM) are also very common in patients with lung and breast cancer, and occur in ∼20-40% of patients across different cancer types. Metastases in the brain are associated with poor prognosis due to the lack of efficient therapies. In the past, patients with BrM used to be excluded from immune-based clinical trials due to the assumption that such therapies may not work in the context of "immune-specialized" environment in the brain, or may cause harm. However, recent trials in patients with BrM demonstrated safety and intracranial activity of anti-PD-1 and anti-CTLA-4 therapy. We here discuss how immune checkpoint therapy works in BrM, with focus on T cells and the cross-talk between BrM, the immune system, and tumors growing outside the brain. We discuss major open questions in our understanding of what is required for an effective immune checkpoint inhibitor therapy in BrM.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Lorger M,Andreou T,Fife C,James Fdoi
10.3389/fnmol.2019.00282subject
Has Abstractpub_date
2019-11-21 00:00:00pages
282issn
1662-5099journal_volume
12pub_type
杂志文章,评审abstract::ADP-ribosylation of the P2X7k splice variant on mouse T cells by Ecto-ADP-ribosyltransferase ARTC2.2 in response to its substrate extracellular nicotinamide adenine dinucleotide (NAD+) triggers cell death. Since NAD+ is released as a danger signal during tissue damage, this NAD+-induced cell death (NICD) may impact th...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00330
更新日期:2020-01-14 00:00:00
abstract::The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across the time of cortical foldi...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00031
更新日期:2017-02-09 00:00:00
abstract::The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00055
更新日期:2017-03-02 00:00:00
abstract::Following the discovery that the amyloid precursor protein (APP) is the source of β-amyloid peptides (Aβ) that accumulate in Alzheimer's disease (AD), structural analyses suggested that the holoprotein resembles a transmembrane receptor. Initial studies using reconstituted membranes demonstrated that APP can directly ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00003
更新日期:2017-01-31 00:00:00
abstract::Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity. The members of the zinc-finger transcription factor fami...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.00051
更新日期:2020-04-08 00:00:00
abstract::Long-term potentiation (LTP) and long-term depression (LTD) are two major forms of synaptic plasticity that are widely accepted as cellular mechanisms involved in learning and memory. Metaplasticity is a process whereby modifications in synaptic processes shift the threshold for subsequent plasticity. While metaplasti...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00322
更新日期:2020-01-24 00:00:00
abstract::Following axotomy, the activation of multiple intracellular signaling cascades causes the expression of a cocktail of regeneration-associated transcription factors which interact with each other to determine the fate of the injured neurons. The nerve injury response is channeled through manifold and parallel pathways,...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2012.00008
更新日期:2012-02-10 00:00:00
abstract::The ubiquitous metabolic intermediary and nucleoside adenosine is a "master regulator" in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex hom...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00099
更新日期:2016-10-20 00:00:00
abstract::Epilepsy, one of the most prevalent neurological conditions, presents as a complex disorder of network homeostasis characterized by spontaneous non-provoked seizures and associated comorbidities. Currently used antiepileptic drugs have been designed to suppress neuronal hyperexcitability and thereby to suppress epilep...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2016.00026
更新日期:2016-04-13 00:00:00
abstract::Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00369
更新日期:2017-11-15 00:00:00
abstract::Among all organs of an adult animal, the central nervous system stands out because of its vast complexity and morphological diversity. During early development, the entire central nervous system develops from an apparently homogenous group of progenitors that differentiate into all neural cell types. Therefore, unders...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00140
更新日期:2019-05-31 00:00:00
abstract::Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. H...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00156
更新日期:2016-12-21 00:00:00
abstract::The post-synaptic density protein 95 (PSD-95) plays a central role in excitatory synapse development and synaptic plasticity. Phosphorylation of the N-terminus of PSD-95 at threonine 19 (T19) and serine 25 (S25) decreases PSD-95 stability at synapses; however, a molecular mechanism linking PSD-95 phosphorylation to al...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00010
更新日期:2020-03-13 00:00:00
abstract::In the past two decades, yeast models have delivered profound insights into basic mechanisms of protein misfolding and the dysfunction of key cellular pathways associated with amyotrophic lateral sclerosis (ALS). Expressing ALS-associated proteins, such as superoxide dismutase (SOD1), TAR DNA binding protein 43 (TDP-4...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00394
更新日期:2018-10-30 00:00:00
abstract::Alzheimer's disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00239
更新日期:2019-10-11 00:00:00
abstract::Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich r...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00205
更新日期:2018-06-21 00:00:00
abstract::Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying mechanism still remains largely unclear. Here, we found that hypothalamic corticotrophin releasing hormone (CRH) modulates the function of the HPA axis, while hepatec...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00308
更新日期:2017-09-27 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA) are two motoneuron diseases (MNDs) characterized by aberrant protein behavior in affected cells. In familial ALS (fALS) and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00176
更新日期:2017-06-21 00:00:00
abstract::Intracerebral hemorrhage (ICH) is a subtype of stroke with highest mortality and morbidity. We have previously demonstrated that dipotassium bisperoxo (picolinato) oxovanadate (V), (bpV[pic]) inhibits phosphatase and tensin homolog (PTEN) and activates extracellular signal-regulated kinase (ERK)1/2. In this study, we ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00281
更新日期:2019-12-05 00:00:00
abstract::It has been 200 years since Parkinson's disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00225
更新日期:2017-07-18 00:00:00
abstract::Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patte...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00007
更新日期:2020-01-30 00:00:00
abstract::In this review we provide an overview of key in vivo experiments undertaken in the cat spinal cord in the 1950s and 1960s, and point out their contributions to our present understanding of glycine receptor (GlyR) function. Importantly, some of these discoveries were made well before an inhibitory receptor, or its agon...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2010.00013
更新日期:2010-05-21 00:00:00
abstract::The application of super-resolution optical microscopy to investigating synaptic structures has revealed a highly heterogeneous and variable intra-synaptic organization. Dense subsynaptic protein assemblies named subsynaptic domains or SSDs have been proposed as structural units that regulate the efficacy of neuronal ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00161
更新日期:2019-07-02 00:00:00
abstract::Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS)-a relapsing functional bowel disorder-presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resti...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00141
更新日期:2016-12-06 00:00:00
abstract::Glaucoma is a progressive optic neuropathy characterized by visual field defects that ultimately lead to irreversible blindness (Alward, 2000; Anderson et al., 2006). By the year 2020, an estimated 80 million people will have glaucoma, 11 million of which will be bilaterally blind. Primary open-angle glaucoma (POAG) i...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00038
更新日期:2014-05-19 00:00:00
abstract::Neuroblastoma is a neural crest derived malignancy of the peripheral nervous system and is the most common and deadliest tumor of infancy. It is characterized by clinical heterogeneity with a disease spectrum ranging from spontaneous regression without any medical intervention to treatment resistant tumors with metast...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00009
更新日期:2019-01-29 00:00:00
abstract::The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as o...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00132
更新日期:2018-04-24 00:00:00
abstract::Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00125
更新日期:2018-05-15 00:00:00
abstract::Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2014.00093
更新日期:2014-11-27 00:00:00
abstract::Cell signaling in response to an array of diverse stress stimuli converges on the phosphorylation of eukaryotic initiation factor-2α (eIF2α). Evidence is accumulating that persistent eIF2α phosphorylation at Ser51 through prolonged overactivation of regulatory kinases occurs in neurodegenerative diseases such as Alzhe...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00022
更新日期:2014-04-16 00:00:00