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  1. Article ; Online: Macrophage reprogramming for therapy.

    Bart, Valentina M T / Pickering, Robert J / Taylor, Philip R / Ipseiz, Natacha

    Immunology

    2021  Volume 163, Issue 2, Page(s) 128–144

    Abstract: Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although ... ...

    Abstract Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease.
    MeSH term(s) Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; Cell Differentiation ; Cellular Reprogramming ; Humans ; Immunotherapy/trends ; Macrophages/immunology ; Metabolic Diseases/immunology ; Metabolic Diseases/therapy ; Neoplasms/immunology ; Neoplasms/therapy ; Neurodegenerative Diseases/immunology ; Neurodegenerative Diseases/therapy
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.13300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ud II Zs.181: Show issues Location:
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  2. Article ; Online: Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion.

    Lauder, Sarah N / Smart, Kathryn / Bart, Valentina M T / Pires, Ana / Scott, Jake / Milutinovic, Stefan / Godkin, Andrew / Vanhaesebroeck, Bart / Gallimore, Awen

    British journal of cancer

    2022  Volume 127, Issue 9, Page(s) 1595–1602

    Abstract: Background: Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also ... ...

    Abstract Background: Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also has a negative impact on MDSC numbers but the primary mechanism driving this effect has remained unclear.
    Methods: The 4T1 breast cancer mouse model was used in combination with PI-3065 to gain insights into the effect of PI3Kδ inhibition on MDSCs.
    Results: PI-3065 treatment resulted in a concomitant reduction in MDSC expansion and tumour size. However, targeting Tregs independent of PI-3065 was also associated with reduced tumour volume and MDSC numbers. Surgical removal of tumours resulted in a rapid and significant decline in MDSC numbers, whilst ex vivo studies using cells from PI-3065-treated mice demonstrated no direct effect of the inhibitor on MDSC activity.
    Conclusions: Our data suggest that MDSCs are not inhibited directly by PI-3065 treatment but that their reduced recruitment and immunosuppression within the tumour microenvironment is an indirect consequence of PI3Kδ-inhibition-driven tumour control. This indicates that PI3Kδ inhibition drives tumour immunity by breaking down multiple immunosuppressive pathways through both direct mechanisms (on Treg) and indirect mechanisms, secondary to tumour control (on MDSCs).
    MeSH term(s) Animals ; Mice ; Myeloid-Derived Suppressor Cells ; T-Lymphocytes, Regulatory ; Neoplasms ; Tumor Microenvironment ; Cell Proliferation
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-022-01917-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Erratum: Effective

    Ipseiz, Natacha / Czubala, Magdalena A / Bart, Valentina M T / Davies, Luke C / Jenkins, Robert H / Brennan, Paul / Taylor, Philip R

    Molecular therapy. Methods & clinical development

    2020  Volume 19, Page(s) 375

    Abstract: This corrects the article DOI: 10.1016/j.omtm.2019.10.004.]. ...

    Abstract [This corrects the article DOI: 10.1016/j.omtm.2019.10.004.].
    Language English
    Publishing date 2020-11-03
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2020.10.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The role and uses of antibodies in COVID-19 infections: a living review.

    Scourfield, D Oliver / Reed, Sophie G / Quastel, Max / Alderson, Jennifer / Bart, Valentina M T / Teijeira Crespo, Alicia / Jones, Ruth / Pring, Ellie / Richter, Felix Clemens / Burnell, Stephanie E A

    Oxford open immunology

    2021  Volume 2, Issue 1, Page(s) iqab003

    Abstract: Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, ... ...

    Abstract Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2633-6960
    ISSN (online) 2633-6960
    DOI 10.1093/oxfimm/iqab003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Effective

    Ipseiz, Natacha / Czubala, Magdalena A / Bart, Valentina M T / Davies, Luke C / Jenkins, Robert H / Brennan, Paul / Taylor, Philip R

    Molecular therapy. Methods & clinical development

    2019  Volume 16, Page(s) 21–31

    Abstract: Tissue-resident macrophages exhibit specialized phenotypes dependent on ... ...

    Abstract Tissue-resident macrophages exhibit specialized phenotypes dependent on their
    Language English
    Publishing date 2019-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2019.10.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7107: Show issues Location:
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  6. Article ; Online: Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology.

    Rodrigues, Patrícia R S / Alrubayyi, Aljawharah / Pring, Ellie / Bart, Valentina M T / Jones, Ruth / Coveney, Clarissa / Lu, Fangfang / Tellier, Michael / Maleki-Toyserkani, Shayda / Richter, Felix C / Scourfield, D Oliver / Gea-Mallorquí, Ester / Davies, Luke C

    Oxford open immunology

    2020  Volume 1, Issue 1, Page(s) iqaa005

    Abstract: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate ...

    Abstract The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.
    Language English
    Publishing date 2020-12-08
    Publishing country England
    Document type Journal Article
    ISSN 2633-6960
    ISSN (online) 2633-6960
    DOI 10.1093/oxfimm/iqaa005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Innate immunology in COVID-19-a living review. Part I: viral entry, sensing and evasion.

    Coveney, Clarissa / Tellier, Michel / Lu, Fangfang / Maleki-Toyserkani, Shayda / Jones, Ruth / Bart, Valentina M T / Pring, Ellie / Alrubayyi, Aljawharah / Richter, Felix C / Scourfield, D Oliver / Rehwinkel, Jan / Rodrigues, Patrícia R S / Davies, Luke C / Gea-Mallorquí, Ester

    Oxford open immunology

    2020  Volume 1, Issue 1, Page(s) iqaa004

    Abstract: The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer ... ...

    Abstract The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive inflammatory response. Viral evasion strategies directly target anti-viral immunity, counteracting host restriction factors and hijacking signalling pathways to interfere with interferon production. In Part I of this review, we examine SARS-CoV-2 viral entry and the described immune evasion mechanisms to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II.
    Language English
    Publishing date 2020-12-08
    Publishing country England
    Document type Journal Article
    ISSN 2633-6960
    ISSN (online) 2633-6960
    DOI 10.1093/oxfimm/iqaa004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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