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  1. Article: The Potential of Induced Pluripotent Stem Cells to Advance the Treatment of Pancreatic Ductal Adenocarcinoma.

    Krog, Ricki T / de Miranda, Noel F C C / Vahrmeijer, Alexander L / Kooreman, Nigel G

    Cancers

    2021  Volume 13, Issue 22

    Abstract: Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex ... ...

    Abstract Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.
    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13225789
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Author Correction: Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells.

    Zimmermann, Julie / van Haren, Simon D / Diray-Arce, Joann / Adriawan, Ignatius Ryan / Wørzner, Katharina / Krog, Ricki T / Guleed, Safia / Hu, Tu / Mortensen, Rasmus / Dietrich, Jes / Solbak, Sara M Ø / Levy, Ofer / Christensen, Dennis / Pedersen, Gabriel K

    NPJ vaccines

    2024  Volume 9, Issue 1, Page(s) 13

    Language English
    Publishing date 2024-01-11
    Publishing country England
    Document type Published Erratum
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-024-00804-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells.

    Zimmermann, Julie / van Haren, Simon D / Diray-Arce, Joann / Adriawan, Ignatius Ryan / Wørzner, Katharina / Krog, Ricki T / Guleed, Safia / Hu, Tu / Mortensen, Rasmus / Dietrich, Jes / Solbak, Sara M Ø / Levy, Ofer / Christensen, Dennis / Pedersen, Gabriel K

    NPJ vaccines

    2023  Volume 8, Issue 1, Page(s) 189

    Abstract: Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We ... ...

    Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
    Language English
    Publishing date 2023-12-22
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-023-00781-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Local and systemic immune profiles of human pancreatic ductal adenocarcinoma revealed by single-cell mass cytometry.

    Brouwer, Thomas P / de Vries, Natasja L / Abdelaal, Tamim / Krog, Ricki T / Li, Zheng / Ruano, Dina / Fariña, Arantza / Lelieveldt, Boudewijn P F / Morreau, Hans / Bonsing, Bert A / Vahrmeijer, Alexander L / Koning, Frits / de Miranda, Noel F C C

    Journal for immunotherapy of cancer

    2022  Volume 10, Issue 7

    Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in need of effective (immuno)therapeutic treatment strategies. For the optimal application and development of cancer immunotherapies, a comprehensive understanding of ... ...

    Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in need of effective (immuno)therapeutic treatment strategies. For the optimal application and development of cancer immunotherapies, a comprehensive understanding of local and systemic immune profiles in patients with PDAC is required. Here, our goal was to decipher the interplay between local and systemic immune profiles in treatment-naïve patients with PDAC.
    Methods: The immune composition of PDAC, matched non-malignant pancreatic tissue, regional lymph nodes, spleen, portal vein blood, and peripheral blood samples (collected before and after surgery) from 11 patients with PDAC was assessed by measuring 41 immune cell markers by single-cell mass cytometry. Furthermore, the activation potential of tumor-infiltrating lymphocytes as determined by their ability to produce cytokines was investigated by flow cytometry. In addition, the spatial localization of tumor-infiltrating innate lymphocytes in the tumor microenvironment was confirmed by multispectral immunofluorescence.
    Results: We found that CD103
    Conclusions: Our work demonstrates an immunosuppressive landscape in PDAC tissues, generally deprived of cytotoxic T cells and enriched in regulatory T cells and B cells. The antitumor potential of ILC1-like cells in PDAC may be exploited in a therapeutic setting. Importantly, immune profiles detected in blood isolated from the portal vein reflected the immune cell composition of the PDAC microenvironment, suggesting that this anatomical location could be a source of tumor-associated immune cell subsets.
    MeSH term(s) CD8-Positive T-Lymphocytes/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Humans ; Immunotherapy ; Pancreatic Neoplasms/pathology ; Tumor Microenvironment ; Pancreatic Neoplasms
    Language English
    Publishing date 2022-07-06
    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-2022-004638
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Tertiary lymphoid structures critical for prognosis in endometrial cancer patients.

    Horeweg, Nanda / Workel, Hagma H / Loiero, Dominik / Church, David N / Vermij, Lisa / Léon-Castillo, Alicia / Krog, Ricki T / de Boer, Stephanie M / Nout, Remi A / Powell, Melanie E / Mileshkin, Linda R / MacKay, Helen / Leary, Alexandra / Singh, Naveena / Jürgenliemk-Schulz, Ina M / Smit, Vincent T H B M / Creutzberg, Carien L / Koelzer, Viktor H / Nijman, Hans W /
    Bosse, Tjalling / de Bruyn, Marco

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 1373

    Abstract: B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve ... ...

    Abstract B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.
    MeSH term(s) Endometrial Neoplasms/pathology ; Female ; Germinal Center/metabolism ; Humans ; Immunohistochemistry ; Neural Cell Adhesion Molecule L1 ; Tertiary Lymphoid Structures/genetics
    Chemical Substances Neural Cell Adhesion Molecule L1
    Language English
    Publishing date 2022-03-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29040-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients.

    Vietsch, Eveline E / Latifi, Diba / Verheij, Maaike / van der Oost, Elise W A / de Wilde, Roeland F / Haen, Roel / van den Boom, Anne Loes / Koerkamp, Bas Groot / Doornebosch, Pascal G / van Verschuer, Victorien M T / Ooms, Ariadne H A G / Mohammad, Farzana / Willemsen, Marcella / Aerts, Joachim G J V / Krog, Ricki T / de Miranda, Noel F C C / van den Bosch, Thierry P P / Mueller, Yvonne M / Katsikis, Peter D /
    van Eijck, Casper H J

    Frontiers in immunology

    2023  Volume 14, Page(s) 1230306

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with
    MeSH term(s) Humans ; Appendix/microbiology ; Appendix/pathology ; Dysbiosis ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/pathology ; HLA-G Antigens
    Chemical Substances HLA-G Antigens
    Language English
    Publishing date 2023-11-10
    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.2023.1230306
    Database MEDical Literature Analysis and Retrieval System OnLINE

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