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  1. Article ; Online: Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8

    Brownlie, Demi / von Kries, Andreas / Valenzano, Giampiero / Wild, Nicole / Yilmaz, Emel / Säfholm, Jesper / Al-Ameri, Mamdoh / Alici, Evren / Ljunggren, Hans-Gustaf / Schliemann, Igor / Aricak, Ozan / Haglund de Flon, Felix / Michaëlsson, Jakob / Marquardt, Nicole

    Oncoimmunology

    2023  Volume 12, Issue 1, Page(s) 2233402

    Abstract: Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little is known about the spatial distribution of tissue-resident lymphocyte subsets in lung tumors. Using high-parameter flow cytometry, we ... ...

    Abstract Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little is known about the spatial distribution of tissue-resident lymphocyte subsets in lung tumors. Using high-parameter flow cytometry, we identified an accumulation of tissue-resident lymphocytes including tissue-resident NK (trNK) cells and CD8
    MeSH term(s) Humans ; CD8-Positive T-Lymphocytes ; Immunity, Innate ; Integrin alpha1/metabolism ; Lung Neoplasms ; Killer Cells, Natural/metabolism ; Carcinoma, Non-Small-Cell Lung
    Chemical Substances Integrin alpha1
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-402X
    ISSN (online) 2162-402X
    ISSN 2162-402X
    DOI 10.1080/2162402X.2023.2233402
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β.

    Brownlie, Demi / Doughty-Shenton, Dahlia / Yh Soong, Daniel / Nixon, Colin / O Carragher, Neil / M Carlin, Leo / Kitamura, Takanori

    Journal for immunotherapy of cancer

    2021  Volume 9, Issue 1

    Abstract: Background: Metastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor ... ...

    Abstract Background: Metastatic breast cancer is a leading cause of cancer-related death in women worldwide. Infusion of natural killer (NK) cells is an emerging immunotherapy for such malignant tumors, although elimination of the immunosuppressive tumor environment is required to improve its efficacy. The effects of this "metastatic" tumor environment on NK cells, however, remain largely unknown. Previous studies, including our own, have demonstrated that metastasis-associated macrophages (MAMs) are one of the most abundant immune cell types in the metastatic tumor niche in mouse models of metastatic breast cancer. We thus investigated the effects of MAMs on antitumor functions of NK cells in the metastatic tumor microenvironment.
    Methods: MAMs were isolated from the tumor-bearing lung of C57BL/6 mice intravenously injected with E0771-LG mouse mammary tumor cells. The effects of MAMs on NK cell cytotoxicity towards E0771-LG cells were evaluated
    Results: MAMs isolated from the metastatic lung suppressed NK cell-induced tumor cell apoptosis
    Conclusion: This study demonstrates that MAMs are a main negative regulator of NK cell function within the metastatic tumor niche, and MAM targeting is an attractive strategy to improve NK cell-based immunotherapy for metastatic breast cancer.
    MeSH term(s) Adoptive Transfer ; Animals ; Antigens, Ly/metabolism ; Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Female ; Gene Knockout Techniques ; Killer Cells, Natural/immunology ; Killer Cells, Natural/transplantation ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Lung Neoplasms/therapy ; Mice ; Mice, Inbred C57BL ; Natural Cytotoxicity Triggering Receptor 1/metabolism ; Neoplasm Transplantation ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Transforming Growth Factor beta/metabolism ; Tumor-Associated Macrophages/immunology
    Chemical Substances Antigens, Ly ; Csf1r protein, mouse ; Natural Cytotoxicity Triggering Receptor 1 ; Ncr1 protein, mouse ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; Transforming Growth Factor beta
    Language English
    Publishing date 2021-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2020-001740
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Generation of mouse bone marrow-derived macrophages using tumor coculture assays to mimic the tumor microenvironment.

    Güç, Esra / Brownlie, Demi / Rodriguez-Tirado, Carolina / Kitamura, Takanori / Pollard, Jeffrey W

    Methods in enzymology

    2019  Volume 632, Page(s) 91–111

    Abstract: Macrophages are one of the key immune cells within the tumor microenvironment that encourage the growth of tumors at the primary site as well as contributing to all parts of the metastatic cascade. Although it is possible to isolate macrophages directly ... ...

    Abstract Macrophages are one of the key immune cells within the tumor microenvironment that encourage the growth of tumors at the primary site as well as contributing to all parts of the metastatic cascade. Although it is possible to isolate macrophages directly from the tumor, this can be a laborious process and due to their plasticity, it is not possible to maintain their in vivo phenotype in vitro. For this reason, differentiating macrophages from bone marrow is an attractive alternative. Here we present robust methods to study in vitro derived macrophages including (i) the isolation and generation of macrophages from bone marrow, (ii) differentiation/characterization of classically activated, alternatively activated and tumor-conditioned macrophages, as well as (iii) in vitro co-culturing assays for tumor cell-macrophage interaction/transmigration.
    MeSH term(s) Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Cell Differentiation ; Cell Line, Tumor ; Cell Separation/methods ; Cells, Cultured ; Coculture Techniques/methods ; Flow Cytometry/methods ; Macrophages/cytology ; Macrophages/immunology ; Mice ; Neoplasms/immunology ; Tumor Microenvironment
    Language English
    Publishing date 2019-12-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2019.11.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza.

    Brownlie, Demi / Rødahl, Inga / Varnaite, Renata / Asgeirsson, Hilmir / Glans, Hedvig / Falck-Jones, Sara / Vangeti, Sindhu / Buggert, Marcus / Ljunggren, Hans-Gustaf / Michaëlsson, Jakob / Gredmark-Russ, Sara / Smed-Sörensen, Anna / Marquardt, Nicole

    Frontiers in immunology

    2022  Volume 13, Page(s) 834862

    Abstract: Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions ...

    Abstract Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of
    MeSH term(s) COVID-19 ; Gene Expression ; Humans ; Influenza, Human/metabolism ; Killer Cells, Natural ; Lung ; SARS-CoV-2 ; T-Lymphocyte Subsets
    Language English
    Publishing date 2022-03-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.834862
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood.

    Brownlie, Demi / Scharenberg, Marlena / Mold, Jeff E / Hård, Joanna / Kekäläinen, Eliisa / Buggert, Marcus / Nguyen, Son / Wilson, Jennifer N / Al-Ameri, Mamdoh / Ljunggren, Hans-Gustaf / Marquardt, Nicole / Michaëlsson, Jakob

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 11

    Abstract: Human adaptive-like "memory" ... ...

    Abstract Human adaptive-like "memory" CD56
    MeSH term(s) Adaptation, Physiological/immunology ; Flow Cytometry ; Humans ; Immunophenotyping ; Integrin alpha1/immunology ; Killer Cells, Natural/immunology ; Lung/immunology ; Lung Neoplasms/immunology ; Lung Neoplasms/therapy
    Chemical Substances Integrin alpha1
    Language English
    Publishing date 2021-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2016580118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung.

    Alisjahbana, Arlisa / Gao, Yu / Sleiers, Natalie / Evren, Elza / Brownlie, Demi / von Kries, Andreas / Jorns, Carl / Marquardt, Nicole / Michaëlsson, Jakob / Willinger, Tim

    Frontiers in immunology

    2021  Volume 12, Page(s) 752104

    Abstract: Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying ... ...

    Abstract Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Animals ; Animals, Genetically Modified ; CD5 Antigens/immunology ; Cell Differentiation ; Cell Movement ; Cytokines/immunology ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunity, Innate ; Lung/immunology ; Lymphocytes/immunology ; Male ; Mice ; Middle Aged ; Spleen/immunology
    Chemical Substances CD5 Antigens ; Cytokines
    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.752104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Monocytes Differentiate to Immune Suppressive Precursors of Metastasis-Associated Macrophages in Mouse Models of Metastatic Breast Cancer.

    Kitamura, Takanori / Doughty-Shenton, Dahlia / Cassetta, Luca / Fragkogianni, Stamatina / Brownlie, Demi / Kato, Yu / Carragher, Neil / Pollard, Jeffrey W

    Frontiers in immunology

    2018  Volume 8, Page(s) 2004

    Abstract: Metastasis-associated macrophages (MAMs) play pivotal roles in breast cancer metastasis by promoting extravasation and survival of metastasizing cancer cells. In a metastatic breast cancer mouse model, we previously reported that circulating classical ... ...

    Abstract Metastasis-associated macrophages (MAMs) play pivotal roles in breast cancer metastasis by promoting extravasation and survival of metastasizing cancer cells. In a metastatic breast cancer mouse model, we previously reported that circulating classical monocytes (C-MOs) preferentially migrated into the tumor-challenged lung where they differentiated into MAMs. However, the fate and characteristics of C-MOs in the metastatic site has not been defined. In this study, we identified that adoptively transferred C-MOs (F4/80
    Language English
    Publishing date 2018-01-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.02004
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  8. Article ; Online: Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.

    Kitamura, Takanori / Kato, Yu / Brownlie, Demi / Soong, Daniel Y H / Sugano, Gaël / Kippen, Nicolle / Li, Jiufeng / Doughty-Shenton, Dahlia / Carragher, Neil / Pollard, Jeffrey W

    Cancer immunology research

    2019  Volume 7, Issue 12, Page(s) 2052–2064

    Abstract: Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, ... ...

    Abstract Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, the precise mechanisms behind MAM-mediated metastatic tumor outgrowth have not been fully elucidated. Using mouse models of metastatic breast cancer, we showed that MAMs uniquely expressed hepatocyte growth factor (HGF) in metastatic tumors. We also demonstrated that a selected population of cancer cells with high metastatic potential (cancer cells that can establish metastatic tumors in mice with higher number and incidence than parental cells) had higher expression of HGF receptor, MNNG HOS transforming gene (MET), and were more responsive to HGF released from macrophages compared with the parental cells. Blockade of MET signaling in cancer cells suppressed metastatic tumor expansion, in part, through activation of natural killer cells. Results from this study suggest an approach to prevent life-threatening metastatic tumor formation using blockade of MAM-induced MET signal activation in metastatic cancer cells.
    MeSH term(s) Animals ; Cell Line, Tumor ; Female ; Hepatocyte Growth Factor/genetics ; Humans ; Killer Cells, Natural ; Lung/pathology ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Macrophages/metabolism ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism
    Chemical Substances Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
    Language English
    Publishing date 2019-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-19-0234
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Distinct lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza

    Brownlie, Demi / Rødahl, Inga / Varnaite, Renata / Asgeirsson, Hilmir / Glans, Hedvig / Falck-Jones, Sara / Vangeti, Sindhu / Buggert, Marcus / Ljunggren, Hans-Gustaf / Michaëlsson, Jakob / Gredmark-Russ, Sara / Smed-Sörensen, Anna / Marquardt, Nicole

    bioRxiv

    Abstract: Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of ... ...

    Abstract Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, little is known about how blood natural killer (NK) cells and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Using 28-colour flow cytometry and re-analysis of published RNA-seq datasets, we provide a detailed comparative analysis of NK cells and T cells in peripheral blood from moderately sick COVID-19 and influenza patients, focusing on the expression of chemokine receptors known to be involved in leukocyte recruitment to the lung. The results reveal a predominant role for CXCR3, CXCR6, and CCR5 in COVID-19 and influenza patients, mirrored by scRNA-seq signatures in peripheral blood and bronchoalveolar lavage from publicly available datasets. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation as compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza as compared to COVID-19. Together, our results indicate migration of functionally competent CXCR3<sup>+</sup>, CXCR6<sup>+</sup>, and/or CCR5<sup>+</sup> NK cells and T cells to the lungs in moderate COVID-19 and influenza patients, identifying potential common targets for future therapeutic interventions in respiratory viral infections.
    Keywords covid19
    Language English
    Publishing date 2021-01-13
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.01.13.426553
    Database COVID19

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  10. Article ; Online: The Atypical Chemokine Receptor Ackr2 Constrains NK Cell Migratory Activity and Promotes Metastasis.

    Hansell, Christopher A H / Fraser, Alasdair R / Hayes, Alan J / Pingen, Marieke / Burt, Claire L / Lee, Kit Ming / Medina-Ruiz, Laura / Brownlie, Demi / Macleod, Megan K L / Burgoyne, Paul / Wilson, Gillian J / Nibbs, Robert J B / Graham, Gerard J

    Journal of immunology (Baltimore, Md. : 1950)

    2018  Volume 201, Issue 8, Page(s) 2510–2519

    Abstract: Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and ... ...

    Abstract Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1
    MeSH term(s) Animals ; Carcinoma, Lewis Lung ; Cell Movement ; Chemokine CCL2/metabolism ; Cytotoxicity, Immunologic ; Killer Cells, Natural/immunology ; Lectins, C-Type ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasm Metastasis ; Neoplasms, Experimental/immunology ; Receptors, CCR2/metabolism ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism ; Receptors, Immunologic/metabolism
    Chemical Substances Ackr2 protein, mouse ; Ccr2 protein, mouse ; Chemokine CCL2 ; Klrg1 protein, mouse ; Lectins, C-Type ; Receptors, CCR2 ; Receptors, Chemokine ; Receptors, Immunologic
    Language English
    Publishing date 2018-08-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1800131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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