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  1. Article ; Online: Breaching B cell tolerance in the tumor microenvironment.

    Banville, Allyson C / Nelson, Brad H

    Cancer cell

    2022  Volume 40, Issue 4, Page(s) 356–358

    Abstract: The immune system employs complex tolerance mechanisms in order to avoid harmful autoimmunity, yet autoantibodies are frequently observed in cancer. In a paper in Cell, Mazor et al. report that autoantibodies produced by tumor-infiltrating B cells in ... ...

    Abstract The immune system employs complex tolerance mechanisms in order to avoid harmful autoimmunity, yet autoantibodies are frequently observed in cancer. In a paper in Cell, Mazor et al. report that autoantibodies produced by tumor-infiltrating B cells in human ovarian cancer frequently recognize the self-protein matrix metalloproteinase 14 (MMP14) through two distinct mechanisms of tolerance disruption.
    MeSH term(s) Autoantibodies ; Autoimmunity ; B-Lymphocytes ; Humans ; Immune Tolerance ; Tumor Microenvironment
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2022-04-12
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2022.03.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: Show issues Location:
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  2. Article ; Online: Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities.

    Laumont, Céline M / Banville, Allyson C / Gilardi, Mara / Hollern, Daniel P / Nelson, Brad H

    Nature reviews. Cancer

    2022  Volume 22, Issue 7, Page(s) 414–430

    Abstract: Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role ...

    Abstract Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role in tumour control. In many cancers, TIL-Bs have demonstrated strong predictive and prognostic significance in the context of both standard treatments and immune checkpoint blockade, offering the prospect of new therapeutic opportunities that leverage their unique immunological properties. Drawing insights from autoimmunity, we review the molecular phenotypes, architectural contexts, antigen specificities, effector mechanisms and regulatory pathways relevant to TIL-Bs in human cancer. Although the field is young, the emerging picture is that TIL-Bs promote antitumour immunity through their unique mode of antigen presentation to T cells; their role in assembling and perpetuating immunologically 'hot' tumour microenvironments involving T cells, myeloid cells and natural killer cells; and their potential to combat immune editing and tumour heterogeneity through the easing of self-tolerance mechanisms. We end by discussing the most promising approaches to enhance TIL-B responses in concert with other immune cell subsets to extend the reach, potency and durability of cancer immunotherapy.
    MeSH term(s) B-Lymphocytes/pathology ; Humans ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating ; Neoplasms/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2022-04-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-022-00466-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A tumor-restricted glycoform of podocalyxin is a highly selective marker of immunologically cold high-grade serous ovarian carcinoma.

    Brassard, Julyanne / Hughes, Michael R / Dean, Pamela / Hernaez, Diana Canals / Thornton, Shelby / Banville, Allyson C / Smazynski, Julian / Warren, Mary / Zhang, Kevin / Milne, Katy / Gilks, C Blake / Mes-Masson, Anne-Marie / Huntsman, David G / Nelson, Brad H / Roskelley, Calvin D / McNagny, Kelly M

    Frontiers in oncology

    2023  Volume 13, Page(s) 1286754

    Abstract: Introduction: Targeted-immunotherapies such as antibody-drug conjugates (ADC), chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (eg, BiTE: Methods: In this study we characterize these PODO447-expressing tumors as a distinct ... ...

    Abstract Introduction: Targeted-immunotherapies such as antibody-drug conjugates (ADC), chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (eg, BiTE
    Methods: In this study we characterize these PODO447-expressing tumors as a distinct subset of HGSOC using four different patient cohorts that include pre-chemotherapy, post-neoadjuvant chemotherapy (NACT) and relapsing tumors as well as tumors from various peritoneal locations.
    Results: We find that the PODO447 epitope expression is similar across tumor locations and negligibly impacted by chemotherapy. Invariably, tumors with high levels of the PODO447 epitope lack infiltrating CD8
    Discussion: We conclude that the PODO447 glycoepitope is an excellent biomarker of immune "cold" tumors and a candidate for the development of targeted-therapies for these hard-to-treat cancers.
    Language English
    Publishing date 2023-12-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1286754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Co-expression patterns of chimeric antigen receptor (CAR)-T cell target antigens in primary and recurrent ovarian cancer.

    Banville, Allyson C / Wouters, Maartje C A / Oberg, Ann L / Goergen, Krista M / Maurer, Matthew J / Milne, Katy / Ashkani, Jahanshah / Field, Emma / Ghesquiere, Chanel / Jones, Steven J M / Block, Matthew S / Nelson, Brad H

    Gynecologic oncology

    2020  Volume 160, Issue 2, Page(s) 520–529

    Abstract: Objective: Chimeric antigen receptor (CAR)-T cell strategies ideally target a surface antigen that is exclusively and uniformly expressed by tumors; however, no such antigen is known for high-grade serous ovarian carcinoma (HGSC). A potential solution ... ...

    Abstract Objective: Chimeric antigen receptor (CAR)-T cell strategies ideally target a surface antigen that is exclusively and uniformly expressed by tumors; however, no such antigen is known for high-grade serous ovarian carcinoma (HGSC). A potential solution involves combinatorial antigen targeting with AND or OR logic-gating. Therefore, we investigated co-expression of CA125, Mesothelin (MSLN) and Folate Receptor alpha (FOLRA) on individual tumor cells in HGSC.
    Methods: RNA expression of CA125, MSLN, and FOLR1 was assessed using TCGA (HGSC) and GTEx (healthy tissues) databases. Antigen expression profiles and CD3+, CD8+ and CD20+ tumor-infiltrating lymphocyte (TIL) patterns were assessed in primary and recurrent HGSC by multiplex immunofluorescence and immunohistochemistry.
    Results: At the transcriptional level, each antigen was overexpressed in >90% of cases; however, MSLN and FOLR1 showed substantial expression in healthy tissues. At the protein level, CA125 was expressed by the highest proportion of cases and tumor cells per case, followed by MSLN and FOLRA. The most promising pairwise combination was CA125 and/or MSLN (OR gate), with 51.9% of cases containing ≥90% of tumor cells expressing one or both antigens. In contrast, only 5.8% of cases contained ≥90% of tumor cells co-expressing CA125 and MSLN (AND gate). Antigen expression patterns showed modest correlations with TIL. Recurrent tumors retained expression of all three antigens and showed increased TIL densities.
    Conclusions: An OR-gated CAR-T cell strategy against CA125 and MSLN would target the majority of tumor cells in most cases. Antigen expression and T-cell infiltration patterns are favorable for this strategy in primary and recurrent disease.
    MeSH term(s) Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; CA-125 Antigen/immunology ; CA-125 Antigen/metabolism ; Carcinoma, Ovarian Epithelial/immunology ; Carcinoma, Ovarian Epithelial/pathology ; Carcinoma, Ovarian Epithelial/therapy ; Female ; Folate Receptor 1/immunology ; Folate Receptor 1/metabolism ; GPI-Linked Proteins/immunology ; GPI-Linked Proteins/metabolism ; Gene Expression Profiling ; Humans ; Immunotherapy, Adoptive/methods ; Lymphocytes, Tumor-Infiltrating/immunology ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; Ovary/immunology ; Ovary/pathology ; Receptors, Chimeric Antigen/immunology ; Receptors, Chimeric Antigen/metabolism
    Chemical Substances Antigens, Neoplasm ; CA-125 Antigen ; FOLR1 protein, human ; Folate Receptor 1 ; GPI-Linked Proteins ; MUC16 protein, human ; Membrane Proteins ; Receptors, Chimeric Antigen ; mesothelin (J27WDC343N)
    Language English
    Publishing date 2020-12-17
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2020.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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