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  1. Article ; Online: COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade.

    Hansen, Kyle / Kumar, Sandeep / Logronio, Kathryn / Whelan, Sarah / Qurashi, Samir / Cheng, Hsin-Yuan / Drake, Andrew / Tang, Margaret / Wall, Patrick / Bernados, David / Leung, Ling / Ophir, Eran / Alteber, Zoya / Cojocaru, Gady / Galperin, Moran / Frenkel, Masha / White, Mark / Hunter, John / Liang, Spencer C /
    Kotturi, Maya F

    Cancer immunology, immunotherapy : CII

    2021  Volume 70, Issue 12, Page(s) 3525–3540

    Abstract: Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer. However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor ... ...

    Abstract Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer. However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor and member of the DNAM-1 family of immune modulating proteins. We evaluated the prevalence of TIGIT and its cognate ligand, PVR (CD155), in human cancers by assessing their expression in a large set of solid tumors. TIGIT is expressed on CD4
    MeSH term(s) Animals ; Antibodies, Monoclonal/immunology ; B7-H1 Antigen/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Cell Proliferation/physiology ; Female ; Humans ; Immunoglobulin G/immunology ; Immunotherapy/methods ; Jurkat Cells ; Macaca fascicularis ; Mice ; Mice, Inbred BALB C ; Receptors, Cell Surface/immunology ; Receptors, Immunologic/immunology ; Signal Transduction/immunology
    Chemical Substances Antibodies, Monoclonal ; B7-H1 Antigen ; CD274 protein, human ; Immunoglobulin G ; PVRIG protein, human ; Receptors, Cell Surface ; Receptors, Immunologic ; TIGIT protein, human
    Language English
    Publishing date 2021-04-26
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-021-02921-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1237: 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)

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  2. Article ; Online: ILT2 and ILT4 Drive Myeloid Suppression via Both Overlapping and Distinct Mechanisms.

    Tian, Jane / Ashique, Amir M / Weeks, Sabrina / Lan, Tian / Yang, Hong / Chen, Hung-I Harry / Song, Christina / Koyano, Kikuye / Mondal, Kalyani / Tsai, Daniel / Cheung, Isla / Moshrefi, Mehrdad / Kekatpure, Avantika / Fan, Bin / Li, Betty / Qurashi, Samir / Rocha, Lauren / Aguayo, Jonathan / Rodgers, Col /
    Meza, Marchelle / Heeke, Darren / Medfisch, Sara M / Chu, Chun / Starck, Shelley / Basak, Nandini Pal / Sankaran, Satish / Malhotra, Mohit / Crawley, Suzanne / Tran, Thomas-Toan / Duey, Dana Y / Ho, Carmence / Mikaelian, Igor / Liu, Wenhui / Rivera, Lee B / Huang, Jiawei / Paavola, Kevin J / O'Hollaren, Kyle / Blum, Lisa K / Lin, Vicky Y / Chen, Peirong / Iyer, Anjushree / He, Sisi / Roda, Julie M / Wang, Yan / Sissons, James / Kutach, Alan K / Kaplan, Daniel D / Stone, Geoffrey W

    Cancer immunology research

    2024  Volume 12, Issue 5, Page(s) 592–613

    Abstract: Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play ...

    Abstract Solid tumors are dense three-dimensional (3D) multicellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune-suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contribution of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that although ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for the optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T-cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune-checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFNγ, and cytolytic T-cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment.
    MeSH term(s) Receptors, Immunologic/metabolism ; Animals ; Humans ; Mice ; Tumor Microenvironment/immunology ; Leukocyte Immunoglobulin-like Receptor B1/metabolism ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Membrane Glycoproteins/metabolism ; Cell Line, Tumor ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Antigens, CD
    Chemical Substances Receptors, Immunologic ; LILRB4 protein, human ; LILRB2 protein, human ; Leukocyte Immunoglobulin-like Receptor B1 ; Membrane Glycoproteins ; LILRB1 protein, human ; LILRB3 protein, human ; Antigens, CD
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article ; 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-23-0568
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7022: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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