001     306240
005     20251118113313.0
024 7 _ |a 10.3390/ijms23094717
|2 doi
024 7 _ |a pmid:35563109
|2 pmid
024 7 _ |a pmc:PMC9105815
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024 7 _ |a 1422-0067
|2 ISSN
024 7 _ |a 1661-6596
|2 ISSN
037 _ _ |a DKFZ-2025-02469
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Iraqi, Muhammed
|0 0000-0001-5488-0996
|b 0
245 _ _ |a Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma.
260 _ _ |a Basel
|c 2022
|b Molecular Diversity Preservation International
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1763461965_1939186
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
|0 0
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500 _ _ |a #DKFZ-MOST-Ca194#
520 _ _ |a 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.
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a NKp44
|2 Other
650 _ 7 |a PCNA
|2 Other
650 _ 7 |a clones
|2 Other
650 _ 7 |a immune check point
|2 Other
650 _ 7 |a multiple myeloma
|2 Other
650 _ 7 |a NCR2 protein, human
|2 NLM Chemicals
650 _ 7 |a Natural Cytotoxicity Triggering Receptor 2
|2 NLM Chemicals
650 _ 7 |a PCNA protein, human
|2 NLM Chemicals
650 _ 7 |a Proliferating Cell Nuclear Antigen
|2 NLM Chemicals
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Killer Cells, Natural
|2 MeSH
650 _ 2 |a Multiple Myeloma: metabolism
|2 MeSH
650 _ 2 |a Natural Cytotoxicity Triggering Receptor 2: metabolism
|2 MeSH
650 _ 2 |a Proliferating Cell Nuclear Antigen: metabolism
|2 MeSH
700 1 _ |a Edri, Avishay
|b 1
700 1 _ |a Greenshpan, Yariv
|b 2
700 1 _ |a Goldstein, Oron
|b 3
700 1 _ |a Ofir, Noa
|0 0000-0002-6600-7745
|b 4
700 1 _ |a Bolel, Priyanka
|b 5
700 1 _ |a Abu Ahmad, Muhammad
|b 6
700 1 _ |a Zektser, Miri
|b 7
700 1 _ |a Campbell, Kerry S
|0 0000-0003-4665-7326
|b 8
700 1 _ |a Rouvio, Ory
|b 9
700 1 _ |a Gazit, Roi
|0 0000-0002-0548-2147
|b 10
700 1 _ |a Porgador, Angel
|b 11
773 _ _ |a 10.3390/ijms23094717
|g Vol. 23, no. 9, p. 4717 -
|0 PERI:(DE-600)2019364-6
|n 9
|p 4717
|t International journal of molecular sciences
|v 23
|y 2022
|x 1422-0067
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