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  1. Article ; Online: Escape from T-cell targeting immunotherapies in acute myeloid leukemia.

    Vadakekolathu, Jayakumar / Rutella, Sergio

    Blood

    2023  

    Abstract: Single-cell and spatial multimodal technologies have propelled discoveries of the solid tumor microenvironment (TME) molecular features and their correlation with clinical response and resistance to immunotherapy. Computational tools are incessantly ... ...

    Abstract Single-cell and spatial multimodal technologies have propelled discoveries of the solid tumor microenvironment (TME) molecular features and their correlation with clinical response and resistance to immunotherapy. Computational tools are incessantly being developed to characterize tumor-infiltrating immune cells and to model tumor immune escape. These advances have led to substantial research into T-cell hypofunctional states in the TME and their reinvigoration with T cell-targeting approaches, including checkpoint inhibitors (CPI). Until recently, we lacked a high-dimensional picture of the acute myeloid leukemia (AML) TME, including compositional and functional differences in immune cells between disease onset and post-chemotherapy or post-transplantation relapse, and the dynamic interplay between immune cells and AML blasts at various maturation stages. AML subgroups with heightened interferon (IFN)-g signaling were shown to derive clinical benefit from CD123 x CD3 bispecific DART molecules and CPI, whilst being less likely to respond to standard-of-care cytotoxic chemotherapy. In this Review, we first highlight recent progress into deciphering immune effector states in AML (including T-cell exhaustion and senescence), oncogenic signaling mechanisms that could reduce the susceptibility of AML cells to T cell-mediated killing and the dichotomous roles of type I and II IFN in anti-tumor immunity. In the second part, we discuss how this knowledge could be translated into opportunities to manipulate the AML TME with the aim to overcome resistance to CPI and other T-cell immunotherapies, building on recent success stories in the solid tumor field, and we provide an outlook for the future.
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023019961
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: IDO1, Cancer and Cancer-Associated Inflammation.

    Rutella, Sergio

    Current medicinal chemistry

    2011  Volume 18, Issue 15, Page(s) 2204

    MeSH term(s) Animals ; Cyclooxygenase 2/immunology ; Gene Expression Regulation ; HIV Infections/enzymology ; HIV Infections/immunology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Neoplasms/enzymology ; Neoplasms/immunology ; T-Lymphocytes, Regulatory/enzymology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Indoleamine-Pyrrole 2,3,-Dioxygenase ; Cyclooxygenase 2 (EC 1.14.99.1)
    Language English
    Publishing date 2011-04-22
    Publishing country United Arab Emirates
    Document type Editorial
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/092986711795656090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4432: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: T-Cell Manipulation Strategies to Prevent Graft-Versus-Host Disease in Haploidentical Stem Cell Transplantation.

    Vadakekolathu, Jayakumar / Rutella, Sergio

    Biomedicines

    2017  Volume 5, Issue 2

    Abstract: Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as ...

    Abstract Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD). More recently, new approaches for mitigating harmful T-cell alloreactivity that mediates GVHD, while preserving the function of tumour-reactive natural killer (NK) cells and γδ T cells, have led to markedly improved clinical outcomes, and are successfully being implemented in the clinic. This article will provide an update on in vitro strategies and in vivo approaches aimed at preventing GVHD by selectively manipulating key components of the adaptive immune response, such as T-cell receptor (TCR)-αβ T cells and CD45RA-expressing naive T cells.
    Language English
    Publishing date 2017-06-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines5020033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Targeting Leukemia Stem Cells in the Bone Marrow Niche.

    Tasian, Sarah K / Bornhäuser, Martin / Rutella, Sergio

    Biomedicines

    2018  Volume 6, Issue 1

    Abstract: ... ...

    Abstract Abst
    Language English
    Publishing date 2018-02-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines6010022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Hypoxia Signaling in Parkinson's Disease: There Is Use in Asking "What HIF?"

    Lestón Pinilla, Laura / Ugun-Klusek, Aslihan / Rutella, Sergio / De Girolamo, Luigi A

    Biology

    2021  Volume 10, Issue 8

    Abstract: Hypoxia is a condition characterized by insufficient tissue oxygenation, which results in impaired oxidative energy production. A reduction in cellular oxygen levels induces the stabilization of hypoxia inducible factor α (HIF-1α), master regulator of ... ...

    Abstract Hypoxia is a condition characterized by insufficient tissue oxygenation, which results in impaired oxidative energy production. A reduction in cellular oxygen levels induces the stabilization of hypoxia inducible factor α (HIF-1α), master regulator of the molecular response to hypoxia, involved in maintaining cellular homeostasis and driving hypoxic adaptation through the control of gene expression. Due to its high energy requirement, the brain is particularly vulnerable to oxygen shortage. Thus, hypoxic injury can cause significant metabolic changes in neural cell populations, which are associated with neurodegeneration. Recent evidence suggests that regulating HIF-1α may ameliorate the cellular damage in neurodegenerative diseases. Indeed, the hypoxia/HIF-1α signaling pathway has been associated to several processes linked to Parkinson's disease (PD) including gene mutations, risk factors and molecular pathways such as mitochondrial dysfunction, oxidative stress and protein degradation impairment. This review will explore the impact of hypoxia and HIF-1α signaling on these specific molecular pathways that influence PD development and will evaluate different novel neuroprotective strategies involving HIF-1α stabilization.
    Language English
    Publishing date 2021-07-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology10080723
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: An Artificial Neural Network Integrated Pipeline for Biomarker Discovery Using Alzheimer's Disease as a Case Study.

    Zafeiris, Dimitrios / Rutella, Sergio / Ball, Graham Roy

    Computational and structural biotechnology journal

    2018  Volume 16, Page(s) 77–87

    Abstract: The field of machine learning has allowed researchers to generate and analyse vast amounts of data using a wide variety of methodologies. Artificial Neural Networks (ANN) are some of the most commonly used statistical models and have been successful in ... ...

    Abstract The field of machine learning has allowed researchers to generate and analyse vast amounts of data using a wide variety of methodologies. Artificial Neural Networks (ANN) are some of the most commonly used statistical models and have been successful in biomarker discovery studies in multiple disease types. This review seeks to explore and evaluate an integrated ANN pipeline for biomarker discovery and validation in Alzheimer's disease, the most common form of dementia worldwide with no proven cause and no available cure. The proposed pipeline consists of analysing public data with a categorical and continuous stepwise algorithm and further examination through network inference to predict gene interactions. This methodology can reliably generate novel markers and further examine known ones and can be used to guide future research in Alzheimer's disease.
    Language English
    Publishing date 2018-02-21
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2018.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Hyperactive neutrophil chemotaxis contributes to anti-tumor necrosis factor-α treatment resistance in inflammatory bowel disease.

    Yau, Tung On / Vadakekolathu, Jayakumar / Foulds, Gemma Ann / Du, Guodong / Dickins, Benjamin / Polytarchou, Christos / Rutella, Sergio

    Journal of gastroenterology and hepatology

    2022  Volume 37, Issue 3, Page(s) 531–541

    Abstract: Background and aim: Anti-tumor necrosis factor-α (anti-TNF-α) agents have been used for inflammatory bowel disease; however, it has up to 30% nonresponse rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient ... ...

    Abstract Background and aim: Anti-tumor necrosis factor-α (anti-TNF-α) agents have been used for inflammatory bowel disease; however, it has up to 30% nonresponse rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNF-α treatment are needed.
    Methods: Publicly available transcriptomic data from inflammatory bowel disease patients receiving anti-TNF-α therapy were systemically collected and integrated. In silico flow cytometry approaches and Metascape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti-TNF-α-treated animal model (with lipopolysaccharide-induced inflammation). The receiver operating characteristic curve was applied to all genes to identify the best prediction biomarkers.
    Results: A total of 449 samples were retrieved from control, baseline, and after primary anti-TNF-α therapy or placebo. No statistically significant differences were observed between anti-TNF-α treatment responders and nonresponders at baseline in immune microenvironment scores. Neutrophil, endothelial cell, and B-cell populations were higher in baseline nonresponders, and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly upregulated in lipopolysaccharide-induced neutrophils, but no statistically significant changes were observed in neutrophils treated with anti-TNF-α. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (receiver operating characteristic curve: 80.7%, 95% confidence interval: 73.8-87.5%), with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in nonresponders compared with responders (P < 0.0001).
    Conclusions: Hyperactive neutrophil chemotaxis influences responses to anti-TNF-α treatment, and IL13RA2 is a potential biomarker to predict anti-TNF-α treatment response.
    MeSH term(s) Animals ; Chemotaxis/physiology ; Drug Resistance ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Neutrophils/physiology ; Tumor Necrosis Factor Inhibitors/pharmacology ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/drug effects
    Chemical Substances Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2022-02-02
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 632882-9
    ISSN 1440-1746 ; 0815-9319
    ISSN (online) 1440-1746
    ISSN 0815-9319
    DOI 10.1111/jgh.15764
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2180: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 299: Show issues

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  8. Article: Reverting Immune Suppression to Enhance Cancer Immunotherapy.

    Guerrouahen, Bella S / Maccalli, Cristina / Cugno, Chiara / Rutella, Sergio / Akporiaye, Emmanuel T

    Frontiers in oncology

    2020  Volume 9, Page(s) 1554

    Abstract: Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, ... ...

    Abstract Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8
    Language English
    Publishing date 2020-01-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2019.01554
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  9. Article: Granulocyte colony-stimulating factor for the induction of T-cell tolerance.

    Rutella, Sergio

    Transplantation

    2007  Volume 84, Issue 1 Suppl, Page(s) S26–30

    Abstract: In recent years, investigators have unraveled a previously unrecognized role for granulocyte colony-stimulating factor (G-CSF) in the regulation of T-cell and dendritic cell functions. The experimental evidence in favor of G-CSF-mediated immune ... ...

    Abstract In recent years, investigators have unraveled a previously unrecognized role for granulocyte colony-stimulating factor (G-CSF) in the regulation of T-cell and dendritic cell functions. The experimental evidence in favor of G-CSF-mediated immune regulation includes the ability to skew T-cell cytokine secretion to T-helper type 2 responses, and to promote regulatory T-cell and tolerogenic dendritic cell differentiation. Accordingly, beneficial effects of G-CSF have been detected in animal models of immune-mediated diseases, including posttransplantation graft-versus-host disease, experimental autoimmune encephalomyelitis, lupus nephritis, inflammatory bowel disease, and diabetes. The growing body of evidence supporting a novel role for G-CSF in the induction of T-cell tolerance is reviewed herein.
    MeSH term(s) Animals ; Cytokines/biosynthesis ; Dendritic Cells/immunology ; Granulocyte Colony-Stimulating Factor/immunology ; Granulocyte Colony-Stimulating Factor/pharmacology ; Humans ; Immune Tolerance/drug effects ; Immune Tolerance/immunology ; Models, Immunological ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology
    Chemical Substances Cytokines ; Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2007-07-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/01.tp.0000269611.66517.bf
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    In stock of ZB MED Cologne/Königswinter

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    Zs.MO 509: Show issues

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  10. Article: Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.

    Alves, Raquel / Gonçalves, Ana Cristina / Rutella, Sergio / Almeida, António M / De Las Rivas, Javier / Trougakos, Ioannis P / Sarmento Ribeiro, Ana Bela

    Cancers

    2021  Volume 13, Issue 19

    Abstract: Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a ... ...

    Abstract Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the
    Language English
    Publishing date 2021-09-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13194820
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