Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma

Muhammed Iraqi, Avishay Edri, Yariv Greenshpan, Oron Goldstein, Noa Ofir, Priyanka Bolel, Muhammad Abu Ahmad, Miri Zektser, Kerry S. Campbell, Ory Rouvio, Roi Gazit, Angel Porgador

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Article number4717
JournalInternational Journal of Molecular Sciences
Volume23
Issue number9
DOIs
StatePublished - 1 May 2022

Keywords

  • NKp44
  • PCNA
  • clones
  • immune check point
  • multiple myeloma

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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