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  1. Article: Molecular Imaging of PD-1 Unveils Unknown Characteristics of PD-1 Itself by Visualizing "PD-1 Microclusters".

    Nishi, Wataru / Wakamatsu, Ei / Machiyama, Hiroaki / Matsushima, Ryohei / Yoshida, Yosuke / Nishikawa, Tetsushi / Toyota, Hiroko / Furuhata, Masae / Nishijima, Hitoshi / Takeuchi, Arata / Suzuki, Makoto / Yokosuka, Tadashi

    Advances in experimental medicine and biology

    2024  Volume 1444, Page(s) 197–205

    Abstract: Programmed cell death-1 (PD-1) is one of the most famous coinhibitory receptors that are expressed on effector T cells to regulate their function. The PD-1 ligands, PD-L1 and PD-L2, are expressed by various cells throughout the body at steady state and ... ...

    Abstract Programmed cell death-1 (PD-1) is one of the most famous coinhibitory receptors that are expressed on effector T cells to regulate their function. The PD-1 ligands, PD-L1 and PD-L2, are expressed by various cells throughout the body at steady state and their expression was further regulated within different pathological conditions such as tumor-bearing and chronic inflammatory diseases. In recent years, immune checkpoint inhibitor (ICI) therapies with anti-PD-1 or anti-PD-L1 has become a standard treatment for various malignancies and has shown remarkable antitumor effects. Since the discovery of PD-1 in 1992, a huge number of studies have been conducted to elucidate the function of PD-1. Herein, this paper provides an overview of PD-1 biological findings and sheds some light on the current technology for molecular imaging of PD-1.
    MeSH term(s) Humans ; Programmed Cell Death 1 Receptor/metabolism ; Neoplasms/metabolism ; T-Lymphocytes/metabolism ; B7-H1 Antigen/metabolism ; Immunotherapy/methods ; Molecular Imaging
    Chemical Substances Programmed Cell Death 1 Receptor ; B7-H1 Antigen
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/978-981-99-9781-7_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters.

    Nishi, Wataru / Wakamatsu, Ei / Machiyama, Hiroaki / Matsushima, Ryohei / Saito, Kensho / Yoshida, Yosuke / Nishikawa, Tetsushi / Takehara, Tomohiro / Toyota, Hiroko / Furuhata, Masae / Nishijima, Hitoshi / Takeuchi, Arata / Azuma, Miyuki / Suzuki, Makoto / Yokosuka, Tadashi

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3157

    Abstract: With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into ... ...

    Abstract With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into consideration, but without a standard method to evaluate them. Here we establish an advanced imaging system to visualize human PD-1 microclusters, in which a minimal T cell receptor (TCR) signaling unit co-localizes with the inhibitory co-receptor PD-1 in vitro. In these microclusters PD-1 dephosphorylates both the TCR/CD3 complex and its downstream signaling molecules via the recruitment of a phosphatase, SHP2, upon stimulation with the ligand hPD-L1. In this system, blocking antibodies for hPD-1-hPD-L1 binding inhibits hPD-1 microcluster formation, and each therapeutic antibody (pembrolizumab, nivolumab, durvalumab and atezolizumab) is characterized by a proprietary optimal concentration and combinatorial efficiency enhancement. We propose that our imaging system could digitally evaluate PD-1-mediated T cell suppression to evaluate their clinical usefulness and to develop the most suitable combinations among ICIs or between ICIs and conventional cancer treatments.
    MeSH term(s) Humans ; Programmed Cell Death 1 Receptor ; Single Molecule Imaging ; Nivolumab/pharmacology ; Nivolumab/therapeutic use ; Neoplasms/diagnostic imaging ; Neoplasms/drug therapy ; Receptors, Antigen, T-Cell ; B7-H1 Antigen/metabolism ; Immunotherapy/methods
    Chemical Substances Programmed Cell Death 1 Receptor ; Nivolumab (31YO63LBSN) ; Receptors, Antigen, T-Cell ; B7-H1 Antigen
    Language English
    Publishing date 2023-06-06
    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/s41467-023-38512-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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