Pub Date : 2021-12-31DOI: 10.33696/immunology.3.111
Katherine E. Masih, Jun S. Wei, D. Milewski, Javed Khan
Pediatric neuroblastoma is a heterogenous disease that accounts for significant morbidity and mortality in children. Deep genomic and transcriptomic profiling of patient tumors has revealed a low mutational burden and a paucity of therapeutic targets. Furthermore, different molecular subtypes, such as MYCN amplification, have been associated with adverse outcomes. Using whole transcriptome sequencing, we previously explored the immune microenvironment of neuroblastoma subtypes and discovered its association with clinical outcome. Specifically, we found that patients with tumors infiltrated by higher levels of cytotoxic lymphocytes had a better overall survival. Additionally, we found that a high MYCN gene expression signature in MYCN-non-amplified tumors is an independent predictor of adverse outcome. However, signatures of tumor infiltrating cytotoxic immune cells in this subtype of tumors predict an improved outcome. While this is clinically informative, it does not provide a full picture of the dynamics underlying the biology of tumor immune microenvironment and how to use this information to improve patient outcomes. Here, we highlight our previous work and current approaches using immunotherapy in neuroblastoma and explore our current understanding of the immune biology of these tumors. We further describe how this correlates with patient outcome, and how this information can be used to develop novel immunotherapeutic strategies for pediatric patients with neuroblastoma.
{"title":"Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma","authors":"Katherine E. Masih, Jun S. Wei, D. Milewski, Javed Khan","doi":"10.33696/immunology.3.111","DOIUrl":"https://doi.org/10.33696/immunology.3.111","url":null,"abstract":"Pediatric neuroblastoma is a heterogenous disease that accounts for significant morbidity and mortality in children. Deep genomic and transcriptomic profiling of patient tumors has revealed a low mutational burden and a paucity of therapeutic targets. Furthermore, different molecular subtypes, such as MYCN amplification, have been associated with adverse outcomes. Using whole transcriptome sequencing, we previously explored the immune microenvironment of neuroblastoma subtypes and discovered its association with clinical outcome. Specifically, we found that patients with tumors infiltrated by higher levels of cytotoxic lymphocytes had a better overall survival. Additionally, we found that a high MYCN gene expression signature in MYCN-non-amplified tumors is an independent predictor of adverse outcome. However, signatures of tumor infiltrating cytotoxic immune cells in this subtype of tumors predict an improved outcome. While this is clinically informative, it does not provide a full picture of the dynamics underlying the biology of tumor immune microenvironment and how to use this information to improve patient outcomes. Here, we highlight our previous work and current approaches using immunotherapy in neuroblastoma and explore our current understanding of the immune biology of these tumors. We further describe how this correlates with patient outcome, and how this information can be used to develop novel immunotherapeutic strategies for pediatric patients with neuroblastoma.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"305 - 316"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49253441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-31DOI: 10.33696/immunology.3.112
Sarah Gillaspie, M. Hoffmann
The coronavirus disease 2019 (COVID-19) pandemic places the treating hematologist in a quandary: how best to protect patients with hematologic malignancies from potentially deadly COVID-19 infection while also providing the best therapy for their disease and maximizing opportunities for cure. Cancer patients as a whole trend toward more severe infection and increased mortality from COVID-19 infection. This burden, however, is not equally distributed among all cancer patients and outcomes are particularly poor in those with hematologic malignancies [1]. Lymphodepleting treatments have a profound effect on COVID outcomes; we have recently reported that despite proper and even prolonged quarantine after asymptomatic positive screening test for COVID-19, the initiation of rituximab-based chemotherapy resulted in a delayed respiratory failure in three lymphoma patients [2]. In addition to more severe infection and increased mortality, immunocompromised patients shed virus and remain infectious for far longer than the general population, frequently for several months or longer [3,4]. Finally, to add insult to injury, patients with hematologic malignancies have worse clinical and laboratory responses to vaccines, compromising their ability to be protected against infection and severe disease [5,6]. Prolonged viral shedding, decreased ability to form a durable immune response to vaccination or infection, and subsequent increased probability for severe infection pose a problem for those needing treatment due to progressive disease. Treatment delays in some cases can reduce cure fractions and increase likelihood of disease-related complications. With these cases in mind, there is a need to identify those patients who are at greatest risk of severe infection and determine what steps can we take to minimize the morbidity and mortality associated with both COVID-19 and the hematologic malignancy.
{"title":"COVID-19 Clinical Outcomes and Vaccine Efficacy among Patients with Hematologic Malignancies","authors":"Sarah Gillaspie, M. Hoffmann","doi":"10.33696/immunology.3.112","DOIUrl":"https://doi.org/10.33696/immunology.3.112","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) pandemic places the treating hematologist in a quandary: how best to protect patients with hematologic malignancies from potentially deadly COVID-19 infection while also providing the best therapy for their disease and maximizing opportunities for cure. Cancer patients as a whole trend toward more severe infection and increased mortality from COVID-19 infection. This burden, however, is not equally distributed among all cancer patients and outcomes are particularly poor in those with hematologic malignancies [1]. Lymphodepleting treatments have a profound effect on COVID outcomes; we have recently reported that despite proper and even prolonged quarantine after asymptomatic positive screening test for COVID-19, the initiation of rituximab-based chemotherapy resulted in a delayed respiratory failure in three lymphoma patients [2]. In addition to more severe infection and increased mortality, immunocompromised patients shed virus and remain infectious for far longer than the general population, frequently for several months or longer [3,4]. Finally, to add insult to injury, patients with hematologic malignancies have worse clinical and laboratory responses to vaccines, compromising their ability to be protected against infection and severe disease [5,6]. Prolonged viral shedding, decreased ability to form a durable immune response to vaccination or infection, and subsequent increased probability for severe infection pose a problem for those needing treatment due to progressive disease. Treatment delays in some cases can reduce cure fractions and increase likelihood of disease-related complications. With these cases in mind, there is a need to identify those patients who are at greatest risk of severe infection and determine what steps can we take to minimize the morbidity and mortality associated with both COVID-19 and the hematologic malignancy.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43337470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-31DOI: 10.33696/immunology.3.110
Brandon M. Trainor, N. Shcherbik
The replication of viruses requires host cell functions, specifically for protein synthesis, as viruses lack their own translational machinery. Failure to translate viral mRNAs and generate viral proteins would affect the propagation and evolution of a virus. Thus, independently of their size, complexity, and genomes, viruses evolved sophisticated molecular mechanisms to hijack the translational apparatus of a host in order to recruit ribosomes for efficient protein production. One of the prevalent mechanisms of translation regulation utilized by viruses is non-canonical translation initiation. It is often governed by the 5’-untranslated regions (5’-UTRs) present upstream of a protein-coding sequence in viral mRNAs, such as internal ribosome entry sites (IRESs) and capindependent translation enhancers (CITEs). Viruses can also utilize canonical translation initiation factors of a host in non-canonical ways. Understanding strategies and mechanisms used by viruses to generate proteins is an important task, as it might help develop new therapeutic interventions. We previously have demonstrated that mRNA from the genome of the black beetle virus (BBV) of the Nodaviridae family contains short and unstructured 5’-UTR, which governs translation initiation as a CITE and as a canonical translational enhancer. In this Commentary, we summarize cap-dependent and cap-independent translation initiation mechanisms and further elaborate on the unique ability of the BBV mRNA 5’-UTR to switch between these two modes of translation initiation in the context of the viral life cycle. Medical implications in treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection by targeting viral 5’-UTRs are also discussed.
{"title":"Short and Sweet: Viral 5`-UTR as a Canonical and Non-Canonical Translation Initiation Switch","authors":"Brandon M. Trainor, N. Shcherbik","doi":"10.33696/immunology.3.110","DOIUrl":"https://doi.org/10.33696/immunology.3.110","url":null,"abstract":"The replication of viruses requires host cell functions, specifically for protein synthesis, as viruses lack their own translational machinery. Failure to translate viral mRNAs and generate viral proteins would affect the propagation and evolution of a virus. Thus, independently of their size, complexity, and genomes, viruses evolved sophisticated molecular mechanisms to hijack the translational apparatus of a host in order to recruit ribosomes for efficient protein production. One of the prevalent mechanisms of translation regulation utilized by viruses is non-canonical translation initiation. It is often governed by the 5’-untranslated regions (5’-UTRs) present upstream of a protein-coding sequence in viral mRNAs, such as internal ribosome entry sites (IRESs) and capindependent translation enhancers (CITEs). Viruses can also utilize canonical translation initiation factors of a host in non-canonical ways. Understanding strategies and mechanisms used by viruses to generate proteins is an important task, as it might help develop new therapeutic interventions. We previously have demonstrated that mRNA from the genome of the black beetle virus (BBV) of the Nodaviridae family contains short and unstructured 5’-UTR, which governs translation initiation as a CITE and as a canonical translational enhancer. In this Commentary, we summarize cap-dependent and cap-independent translation initiation mechanisms and further elaborate on the unique ability of the BBV mRNA 5’-UTR to switch between these two modes of translation initiation in the context of the viral life cycle. Medical implications in treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection by targeting viral 5’-UTRs are also discussed.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"296 - 304"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43635749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-31DOI: 10.33696/immunology.3.123
Tyler C. Hammond, Xin Xing, Lucille M. Yanckello, A. Stromberg, Ya-Hsuan Chang, P. Nelson, Ai-Ling Lin
Alzheimer’s disease (AD) is the most common form of dementia with hallmarks of β-amyloid (Aβ) plaques, tau tangles, and neurodegeneration. Studies have shown that neurodegeneration components, especially brain metabolic deficits, are more predictable for AD severity than Aβ and tau. However, detailed knowledge of the biochemical composition of AD brain tissue vs. normal brain tissue remains unclear. In this study, we performed a metabolomics analysis on the brain tissue of 158 community-based older adults in the University of Kentucky AD Research Center brain bank to characterize the biochemical profiles of brains with and without AD based on white/gray matter type, apolipoprotein E genotype (ε3 vs ε4 variants), and disease stage (early vs late) as all these factors influence metabolic processes. We also used machine learning to rank the top metabolites separating controls and AD in gray and white matter. Compared with control samples, we found that glutamate and creatine metabolism were more critical for predicting AD in the gray matter, while glycine, fatty acid, pyrimidine, tricarboxylic acid (TCA) cycle, and phosphatidylcholine metabolism were more critical in the white matter. In ε4 carriers, metabolites associated with the TCA cycle and oxidative phosphorylation were prominent in advanced stages compared to the early stages. In ε3 carriers, metabolites related to oxidative DNA damage, changes in inhibitory neurotransmitters, and disruptions of neuronal membranes were prominent in advanced stages compared to the early stages. In early disease, ε4 carriers had metabolites related to poor kidney function and altered neuronal sterol metabolism compared to ε3 carriers, but there were few differences between genotypes in late disease. Our results indicate that metabolism plays a pivotal role in differentiating APOE- and stage-dependent changes in AD and may facilitate precision lifestyle and dietary interventions to mitigate AD risk in the early stages, especially for ε4 carriers.
{"title":"Human Gray and White Matter Metabolomics to Differentiate APOE and Stage Dependent Changes in Alzheimer’s Disease","authors":"Tyler C. Hammond, Xin Xing, Lucille M. Yanckello, A. Stromberg, Ya-Hsuan Chang, P. Nelson, Ai-Ling Lin","doi":"10.33696/immunology.3.123","DOIUrl":"https://doi.org/10.33696/immunology.3.123","url":null,"abstract":"Alzheimer’s disease (AD) is the most common form of dementia with hallmarks of β-amyloid (Aβ) plaques, tau tangles, and neurodegeneration. Studies have shown that neurodegeneration components, especially brain metabolic deficits, are more predictable for AD severity than Aβ and tau. However, detailed knowledge of the biochemical composition of AD brain tissue vs. normal brain tissue remains unclear. In this study, we performed a metabolomics analysis on the brain tissue of 158 community-based older adults in the University of Kentucky AD Research Center brain bank to characterize the biochemical profiles of brains with and without AD based on white/gray matter type, apolipoprotein E genotype (ε3 vs ε4 variants), and disease stage (early vs late) as all these factors influence metabolic processes. We also used machine learning to rank the top metabolites separating controls and AD in gray and white matter. Compared with control samples, we found that glutamate and creatine metabolism were more critical for predicting AD in the gray matter, while glycine, fatty acid, pyrimidine, tricarboxylic acid (TCA) cycle, and phosphatidylcholine metabolism were more critical in the white matter. In ε4 carriers, metabolites associated with the TCA cycle and oxidative phosphorylation were prominent in advanced stages compared to the early stages. In ε3 carriers, metabolites related to oxidative DNA damage, changes in inhibitory neurotransmitters, and disruptions of neuronal membranes were prominent in advanced stages compared to the early stages. In early disease, ε4 carriers had metabolites related to poor kidney function and altered neuronal sterol metabolism compared to ε3 carriers, but there were few differences between genotypes in late disease. Our results indicate that metabolism plays a pivotal role in differentiating APOE- and stage-dependent changes in AD and may facilitate precision lifestyle and dietary interventions to mitigate AD risk in the early stages, especially for ε4 carriers.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"397 - 412"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69670469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-31DOI: 10.33696/immunology.3.124
E. Bergen, S. Mastbergen, F. Lafeber, R. Schutgens, L. Vulpen
Hemophilia is a rare congenital bleeding disorder caused by a lack of or diminished activity of clotting factor VIII (hemophilia A) or IX (hemophilia B). This deficiency leads to an increase in spontaneous and traumatic bleeding especially in the large hinged joints. Joint bleeding may result in synovial inflammation and cartilage/bone damage, ultimately leading to irreversible hemophilic arthropathy (HA) [1]. Preventing hemarthroses and accurately monitoring joint status once arthropathy has developed, is of utmost importance to prevent invalidating arthropathy and subsequent major orthopedic interventions.
{"title":"Joint Health Markers in Hemophilia: The State of the Art","authors":"E. Bergen, S. Mastbergen, F. Lafeber, R. Schutgens, L. Vulpen","doi":"10.33696/immunology.3.124","DOIUrl":"https://doi.org/10.33696/immunology.3.124","url":null,"abstract":"Hemophilia is a rare congenital bleeding disorder caused by a lack of or diminished activity of clotting factor VIII (hemophilia A) or IX (hemophilia B). This deficiency leads to an increase in spontaneous and traumatic bleeding especially in the large hinged joints. Joint bleeding may result in synovial inflammation and cartilage/bone damage, ultimately leading to irreversible hemophilic arthropathy (HA) [1]. Preventing hemarthroses and accurately monitoring joint status once arthropathy has developed, is of utmost importance to prevent invalidating arthropathy and subsequent major orthopedic interventions.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41455245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-31DOI: 10.33696/immunology.3.115
Mark E Issa, C. Rudd
The serine/threonine kinase, glycogen synthase kinase 3 (GSK-3) has been implicated in immune cell activation and function. Our recent studies have shown that the abrogation of GSK-3 activity down-regulates the expression of key inhibitory receptors PD-1 and LAG-3. It also regulates the expression of the transcription factor NFAT which, in turn, is responsible for inhibiting PD-1/LAG-3 transcription as well as activating the expression of cytolytic effector proteins such as perforin and granzyme B. The role of components of the Wnt signaling pathway in these events remains to be fully uncovered. This mini-review discusses the recent discoveries that have elucidated the role of the GSK-3 signaling pathway in cancer immunotherapy.
{"title":"Glycogen Synthase Kinase-3 (GSK-3) Regulation of Inhibitory Coreceptor Expression in T-cell Immunity","authors":"Mark E Issa, C. Rudd","doi":"10.33696/immunology.3.115","DOIUrl":"https://doi.org/10.33696/immunology.3.115","url":null,"abstract":"The serine/threonine kinase, glycogen synthase kinase 3 (GSK-3) has been implicated in immune cell activation and function. Our recent studies have shown that the abrogation of GSK-3 activity down-regulates the expression of key inhibitory receptors PD-1 and LAG-3. It also regulates the expression of the transcription factor NFAT which, in turn, is responsible for inhibiting PD-1/LAG-3 transcription as well as activating the expression of cytolytic effector proteins such as perforin and granzyme B. The role of components of the Wnt signaling pathway in these events remains to be fully uncovered. This mini-review discusses the recent discoveries that have elucidated the role of the GSK-3 signaling pathway in cancer immunotherapy.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"336 - 342"},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46848278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-23DOI: 10.33696/immunology.3.118
D. Sheikh-Hamad, Michael W. Holliday, Qingtian Li
The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-β) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.
{"title":"Megalin-Mediated Trafficking of Mitochondrial Intracrines: Relevance to Signaling and Metabolism","authors":"D. Sheikh-Hamad, Michael W. Holliday, Qingtian Li","doi":"10.33696/immunology.3.118","DOIUrl":"https://doi.org/10.33696/immunology.3.118","url":null,"abstract":"The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-β) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"3 1","pages":"364 - 369"},"PeriodicalIF":0.0,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47858126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-β) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.
{"title":"Megalin-Mediated Trafficking of Mitochondrial Intracrines: Relevance to Signaling and Metabolism.","authors":"David Sheikh-Hamad, Michael Holliday, Qingtian Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-β) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":"364-369"},"PeriodicalIF":0.0,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39873894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-10DOI: 10.33696/immunology.3.107
Erwan Poivet, M. Daniel, F. Bozza, T. Sharshar, Pierre-Marie, Lledó
Erwan Poivet1#, Matthieu Daniel2#, Fernando A. Bozza3, Tarek Sharshar2*, Pierre-Marie Lledo1* 1Laboratory for Perception and Memory, Institut Pasteur, CNRS UMR3571, 25, rue du Docteur Roux, Paris, 75724, Cedex 15, France 2Neuro-anesthesiology and Intensive Care Medicine, GHU-Psychiatrie et Neurosciences, Université de Paris, Paris, France 3National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation (FIOCRUZ), and D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil #These authors contributed equally
Erwan Poivet1#，Matthieu Daniel2#，Fernando A.Bozza3，Tarek Sharshar2*，Pierre Marie Lledo1*1巴斯德研究所感知与记忆实验室，CNRS UMR3571，25，rue du Docteur Roux，Paris，75724，Cedex 15，法国2欧洲麻醉学和重症监护医学，GHU精神病学和神经科学，巴黎大学，巴黎，法国3国家传染病研究所Evandro Chagas，Oswaldo Cruz基金会（FIOCRUZ）和D’Or研究与教育研究所（IDOR），巴西里约热内卢#这些作者的贡献相等
{"title":"Neurological Manifestations Associated with SARS-CoV-2 Invasion of the Autonomous Nervous System","authors":"Erwan Poivet, M. Daniel, F. Bozza, T. Sharshar, Pierre-Marie, Lledó","doi":"10.33696/immunology.3.107","DOIUrl":"https://doi.org/10.33696/immunology.3.107","url":null,"abstract":"Erwan Poivet1#, Matthieu Daniel2#, Fernando A. Bozza3, Tarek Sharshar2*, Pierre-Marie Lledo1* 1Laboratory for Perception and Memory, Institut Pasteur, CNRS UMR3571, 25, rue du Docteur Roux, Paris, 75724, Cedex 15, France 2Neuro-anesthesiology and Intensive Care Medicine, GHU-Psychiatrie et Neurosciences, Université de Paris, Paris, France 3National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation (FIOCRUZ), and D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil #These authors contributed equally","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48247778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-10DOI: 10.33696/immunology.3.109
J. Zang, Haiqing Dong
Tumor immunotherapy, including monoclonal antibody of immune checkpoint blockade, therapeutic antibody, cancer vaccine and cell therapy, etc., is to restart and maintain the tumor immune cycle, restore the normal antitumor immune response of the body, so as to control and eliminate the tumor [1,2]. Among them, tumor vaccine, which can elicit robust immune response and produce sustained immune memory effect, is particularly favored in the treatment and prevention of tumor recurrence [3,4]. Notably, compared with specific antigen vaccine, whole cell vaccine does not need complex antigen screening and purification process, and can provide all antigens of specific tumor, so it has great prospects [5,6]. Nevertheless, the immune effect of whole cell vaccine is not satisfactory because of its low immunogenicity and limitation efficiency of antigen presentation [7,8].
{"title":"Commentary on “A Vaccine for Photodynamic Immunogenic Cell Death: Tumor Cell Caged b y Cellular Disulfide–Thiol Exchange for Immunotherapy”","authors":"J. Zang, Haiqing Dong","doi":"10.33696/immunology.3.109","DOIUrl":"https://doi.org/10.33696/immunology.3.109","url":null,"abstract":"Tumor immunotherapy, including monoclonal antibody of immune checkpoint blockade, therapeutic antibody, cancer vaccine and cell therapy, etc., is to restart and maintain the tumor immune cycle, restore the normal antitumor immune response of the body, so as to control and eliminate the tumor [1,2]. Among them, tumor vaccine, which can elicit robust immune response and produce sustained immune memory effect, is particularly favored in the treatment and prevention of tumor recurrence [3,4]. Notably, compared with specific antigen vaccine, whole cell vaccine does not need complex antigen screening and purification process, and can provide all antigens of specific tumor, so it has great prospects [5,6]. Nevertheless, the immune effect of whole cell vaccine is not satisfactory because of its low immunogenicity and limitation efficiency of antigen presentation [7,8].","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44565009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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