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Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma.
Iraqi, Muhammed; Edri, Avishay; Greenshpan, Yariv; Goldstein, Oron; Ofir, Noa; Bolel, Priyanka; Abu Ahmad, Muhammad; Zektser, Miri; Campbell, Kerry S; Rouvio, Ory; Gazit, Roi; Porgador, Angel.
Afiliación
  • Iraqi M; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Edri A; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Greenshpan Y; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Goldstein O; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Ofir N; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Bolel P; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Abu Ahmad M; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Zektser M; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Campbell KS; The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • Rouvio O; Internal Medicine A and Multiple Myeloma Clinic, Soroka Medical Center, Beer Sheva 8489501, Israel.
  • Gazit R; Blood Cell Development and Host Defense Program, Research Institute at Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Porgador A; Internal Medicine A and Multiple Myeloma Clinic, Soroka Medical Center, Beer Sheva 8489501, Israel.
Int J Mol Sci ; 23(9)2022 Apr 25.
Article en En | MEDLINE | ID: mdl-35563109
Multiple Myeloma (MM) is a devastating malignancy that evades immune destruction using multiple mechanisms. The NKp44 receptor interacts with PCNA (Proliferating Cell Nuclear Antigen) and may inhibit NK cells' functions. Here we studied in vitro the expression and function of PCNA on MM cells. First, we show that PCNA is present on the cell membrane of five out of six MM cell lines, using novel anti-PCNA mAb developed to recognize membrane-associated PCNA. Next, we stained primary bone marrow (BM) mononuclear cells from MM patients and showed significant staining of membrane-associated PCNA in the fraction of CD38+CD138+ BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN-γ-secretion and degranulation. Our results highlight the possible blocking of the NKp44-PCNA immune checkpoint by the mAb 14-25-9 antibody to enhance NK cell responses against MM, providing a novel treatment option.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mieloma Múltiple Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mieloma Múltiple Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza