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Book ; Online ; Thesis: Impact of IL-6 classic- and IL-6 trans-signaling on Concanavalin A immune-mediated liver damage

Malchow, Sven [Verfasser]

2010

Author's details	Sven Malchow
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Universitätsbibliothek Kiel
Publishing place	Kiel
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Shaping the repertoire of tumor-infiltrating effector and regulatory T cells.

Savage, Peter A / Leventhal, Daniel S / Malchow, Sven

Immunological reviews

2014 Volume 259, Issue 1, Page(s) 245–258

Abstract: Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T-cell-mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve ... ...

Abstract	Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T-cell-mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve within the context of self-tissues, the immune mechanisms that prevent the autoimmune attack of normal tissues function in parallel to restrict anti-tumor immunity. In particular, the purging of autoreactive T cells and the development of immune-suppressive regulatory T cells (Tregs) are thought to be major barriers impeding anti-tumor immune responses. Here, we discuss current understanding regarding the antigens recognized by tumor-infiltrating T-cell populations, the mechanisms that shape the repertoire of these cells, and the role of the transcription factor autoimmune regulator (Aire) in these processes. Further elucidation of these principles is likely to be critical for optimizing emerging cancer immunotherapies, and for the rational design of novel therapies exhibiting robust anti-tumor activity with limited toxicity.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology ; Antigens, Neoplasm/immunology ; Autoimmunity/genetics ; Autoimmunity/immunology ; Clonal Selection, Antigen-Mediated/genetics ; Clonal Selection, Antigen-Mediated/immunology ; Epitopes, T-Lymphocyte ; Female ; Humans ; Immune Tolerance ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Male ; Mice ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Prostate/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Thymus Gland/immunology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Microenvironment/immunology ; AIRE Protein
Chemical Substances	Antigens, Neoplasm ; Epitopes, T-Lymphocyte ; Transcription Factors
Language	English
Publishing date	2014-04-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12166
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Organ-specific regulatory T cells of thymic origin are expanded in murine prostate tumors.

Malchow, Sven / Leventhal, Daniel S / Savage, Peter A

Oncoimmunology

2013 Volume 2, Issue 7, Page(s) e24898

Abstract: Little is known about the relative contributions of self-specific regulatory T cells (Tregs) of thymic origin and induced Tregs generated extrathymically to the pool of tumor-infiltrating Tregs. We have recently demonstrated that thymic-derived Tregs ... ...

Abstract	Little is known about the relative contributions of self-specific regulatory T cells (Tregs) of thymic origin and induced Tregs generated extrathymically to the pool of tumor-infiltrating Tregs. We have recently demonstrated that thymic-derived Tregs reactive to a prostate-associated self antigen are highly and recurrently enriched within oncogene-driven murine prostate cancers.
Language	English
Publishing date	2013-05-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.24898
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online ; Thesis: Impact of IL-6 classic- and IL-6 trans-signaling on Concanavalin A immune-mediated liver damage

Malchow, Sven / Rose-John, Stefan

2010

Title variant	Einfluss von IL-6 klassik- und IL-6 trans-signaling auf Concanavalin A immunvermittelten Leberschaden
Author's details	Sven Malchow
Language	English
Size	Online-Ressource
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Kiel, 2010
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Basic principles of tumor-associated regulatory T cell biology.

Savage, Peter A / Malchow, Sven / Leventhal, Daniel S

Trends in immunology

2012 Volume 34, Issue 1, Page(s) 33–40

Abstract: Due to the critical role of forkhead box (Fox)p3(+) regulatory T cells (Tregs) in the regulation of immunity and the enrichment of Tregs within many human tumors, several emerging therapeutic strategies for cancer involve the depletion or modulation of ... ...

Abstract	Due to the critical role of forkhead box (Fox)p3(+) regulatory T cells (Tregs) in the regulation of immunity and the enrichment of Tregs within many human tumors, several emerging therapeutic strategies for cancer involve the depletion or modulation of Tregs, with the aim of eliciting enhanced antitumor immune responses. Here, we review recent advances in understanding of the fundamental biology of Tregs, and discuss the implications of these findings for current models of tumor-associated Treg biology. In particular, we discuss the context-dependent functional diversity of Tregs, the developmental origins of these cells, and the nature of the antigens that they recognize within the tumor environment. In addition, we highlight critical areas of focus for future research.
MeSH term(s)	Animals ; Antigens/immunology ; Cell Lineage ; Cell Movement ; Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Antigens
Language	English
Publishing date	2012-09-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2012.08.005
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Article: Circulating Autoantibodies Recognizing Immunodominant Epitopes From Human Apolipoprotein B Associate With Cardiometabolic Risk Factors, but Not With Atherosclerotic Disease.

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 826729

Abstract: Rationale: Atherosclerosis is a chronic inflammatory disease of large arteries that involves an autoimmune response with autoreactive T cells and auto-antibodies recognizing Apolipoprotein B (ApoB), the core protein of low-density lipoprotein (LDL). ... ...

Abstract	Rationale: Atherosclerosis is a chronic inflammatory disease of large arteries that involves an autoimmune response with autoreactive T cells and auto-antibodies recognizing Apolipoprotein B (ApoB), the core protein of low-density lipoprotein (LDL). Here, we aimed to establish a clinical association between circulating human ApoB auto-antibodies with atherosclerosis and its clinical risk factors using a novel assay to detect auto-antibodies against a pool of highly immunogenic ApoB-peptides. Methods and results: To detect polyclonal IgM- and IgG-antibodies recognizing ApoB, we developed a chemiluminescent sandwich ELISA with 30 ApoB peptides selected by an Conclusion: Using a novel ELISA method to detect auto-antibodies against ApoB in humans, we show that anti-ApoB IgG associate with cardiovascular risk factors but not with the clinical appearance of atherosclerosis, suggesting that humoral immune responses against ApoB are shaped by cardiovascular risk factors but not disease status itself. This novel tool will be helpful to develop immune-based risk stratification for clinical atherosclerosis in the future.
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.826729
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The HPK1 Inhibitor A-745 Verifies the Potential of Modulating T Cell Kinase Signaling for Immunotherapy.

ACS chemical biology

2022 Volume 17, Issue 3, Page(s) 556–566

Abstract: Hematopoietic progenitor kinase 1 (HPK1) is an MAP4K family member within the Ste20-like serine/threonine branch of the kinome. HPK1 expression is limited to hematopoietic cells and has a predominant role as a negative regulator of T cell function. ... ...

Abstract	Hematopoietic progenitor kinase 1 (HPK1) is an MAP4K family member within the Ste20-like serine/threonine branch of the kinome. HPK1 expression is limited to hematopoietic cells and has a predominant role as a negative regulator of T cell function. Because of the central/dominant role in negatively regulating T cell function, HPK1 has long been in the center of interest as a potential pharmacological target for immune therapy. The development of a small molecule HPK1 inhibitor remains challenging because of the need for high specificity relative to other kinases, including additional MAP4K family members, that are required for efficient immune cell activation. Here, we report the identification of the selective and potent HPK1 chemical probe, A-745. In unbiased cellular kinase-binding assays, A-745 demonstrates an excellent cellular selectivity binding profile within pharmacologically relevant concentrations. This HPK1 selectivity translates to an
MeSH term(s)	Immunologic Factors ; Immunotherapy ; Protein Serine-Threonine Kinases ; Signal Transduction ; T-Lymphocytes
Chemical Substances	Immunologic Factors ; hematopoietic progenitor kinase 1 (EC 2.7.1.11) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.1c00819
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage.

Malchow, Sven / Leventhal, Daniel S / Lee, Victoria / Nishi, Saki / Socci, Nicholas D / Savage, Peter A

Immunity

2016 Volume 44, Issue 5, Page(s) 1102–1113

Abstract: The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by autoimmune regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both ... ...

Abstract	The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by autoimmune regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both clonal deletion and the development of Foxp3(+) regulatory T (Treg) cells, suggesting that autoimmunity associated with Aire deficiency results from two failed tolerance mechanisms. Here, examination of autoimmune lesions in Aire(-/-) mice revealed an unexpected third possibility. We found that the predominant conventional T cell clonotypes infiltrating target lesions express antigen receptors that were preferentially expressed by Foxp3(+) Treg cells in Aire(+/+) mice. Thus, Aire enforces immune tolerance by ensuring that distinct autoreactive T cell specificities differentiate into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.
MeSH term(s)	Animals ; Autoantigens/immunology ; Autoimmunity/genetics ; Cell Differentiation ; Cell Lineage ; Clonal Deletion ; Clonal Selection, Antigen-Mediated ; Clone Cells ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Immune Tolerance/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Prostate/immunology ; T-Cell Antigen Receptor Specificity ; T-Lymphocyte Subsets/physiology ; T-Lymphocytes, Regulatory/physiology ; Thymus Gland/immunology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; AIRE Protein
Chemical Substances	Autoantigens ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Transcription Factors
Language	English
Publishing date	2016-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2016.02.009
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Basic principles of tumor-associated regulatory T cell biology

Savage, Peter A / Malchow, Sven / Leventhal, Daniel S

Trends in immunology. 2013 Jan., v. 34, no. 1

2013

Abstract: Due to the critical role of forkhead box (Fox)p3⁺ regulatory T cells (Tregs) in the regulation of immunity and the enrichment of Tregs within many human tumors, several emerging therapeutic strategies for cancer involve the depletion or modulation of ... ...

Abstract	Due to the critical role of forkhead box (Fox)p3⁺ regulatory T cells (Tregs) in the regulation of immunity and the enrichment of Tregs within many human tumors, several emerging therapeutic strategies for cancer involve the depletion or modulation of Tregs, with the aim of eliciting enhanced antitumor immune responses. Here, we review recent advances in understanding of the fundamental biology of Tregs, and discuss the implications of these findings for current models of tumor-associated Treg biology. In particular, we discuss the context-dependent functional diversity of Tregs, the developmental origins of these cells, and the nature of the antigens that they recognize within the tumor environment. In addition, we highlight critical areas of focus for future research.
Keywords	T-lymphocytes ; antigens ; functional diversity ; humans ; immune response ; models ; neoplasms
Language	English
Dates of publication	2013-01
Size	p. 33-40.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2012.08.005
Database	NAL-Catalogue (AGRICOLA)

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Article: The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research.

Krčmář, Lenka / Jäger, Iris / Boudriot, Emanuel / Hanken, Katharina / Gabriel, Vanessa / Melcher, Julian / Klimas, Nicole / Dengl, Fanny / Schmoelz, Susanne / Pingen, Pauline / Campana, Mattia / Moussiopoulou, Joanna / Yakimov, Vladislav / Ioannou, Georgios / Wichert, Sven / DeJonge, Silvia / Zill, Peter / Papazov, Boris / de Almeida, Valéria /

Galinski, Sabrina / Gabellini, Nadja / Hasanaj, Genc / Mortazavi, Matin / Karali, Temmuz / Hisch, Alexandra / Kallweit, Marcel S / Meisinger, Verena J / Löhrs, Lisa / Neumeier, Karin / Behrens, Stephanie / Karch, Susanne / Schworm, Benedikt / Kern, Christoph / Priglinger, Siegfried / Malchow, Berend / Steiner, Johann / Hasan, Alkomiet / Padberg, Frank / Pogarell, Oliver / Falkai, Peter / Schmitt, Andrea / Wagner, Elias / Keeser, Daniel / Raabe, Florian J

Frontiers in psychiatry

2023 Volume 14, Page(s) 1179811

Abstract: Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized ...

Abstract	Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis. Methods: In line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes Results: Here, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives. Discussion: The identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2023.1179811
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