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000306240 0247_ $$2doi$$a10.3390/ijms23094717
000306240 0247_ $$2pmid$$apmid:35563109
000306240 0247_ $$2pmc$$apmc:PMC9105815
000306240 0247_ $$2ISSN$$a1422-0067
000306240 0247_ $$2ISSN$$a1661-6596
000306240 037__ $$aDKFZ-2025-02469
000306240 041__ $$aEnglish
000306240 082__ $$a540
000306240 1001_ $$00000-0001-5488-0996$$aIraqi, Muhammed$$b0
000306240 245__ $$aBlocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma.
000306240 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2022
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000306240 520__ $$aMultiple Myeloma (MM) is a devastating malignancy that evades immune destruction using multiple mechanisms. The NKp44 receptor interacts with PCNA (Proliferating Cell Nuclear Antigen) and may inhibit NK cells' functions. Here we studied in vitro the expression and function of PCNA on MM cells. First, we show that PCNA is present on the cell membrane of five out of six MM cell lines, using novel anti-PCNA mAb developed to recognize membrane-associated PCNA. Next, we stained primary bone marrow (BM) mononuclear cells from MM patients and showed significant staining of membrane-associated PCNA in the fraction of CD38+CD138+ BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN-γ-secretion and degranulation. Our results highlight the possible blocking of the NKp44-PCNA immune checkpoint by the mAb 14-25-9 antibody to enhance NK cell responses against MM, providing a novel treatment option.
000306240 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000306240 650_7 $$2Other$$aNKp44
000306240 650_7 $$2Other$$aPCNA
000306240 650_7 $$2Other$$aclones
000306240 650_7 $$2Other$$aimmune check point
000306240 650_7 $$2Other$$amultiple myeloma
000306240 650_7 $$2NLM Chemicals$$aNCR2 protein, human
000306240 650_7 $$2NLM Chemicals$$aNatural Cytotoxicity Triggering Receptor 2
000306240 650_7 $$2NLM Chemicals$$aPCNA protein, human
000306240 650_7 $$2NLM Chemicals$$aProliferating Cell Nuclear Antigen
000306240 650_2 $$2MeSH$$aCell Line, Tumor
000306240 650_2 $$2MeSH$$aHumans
000306240 650_2 $$2MeSH$$aKiller Cells, Natural
000306240 650_2 $$2MeSH$$aMultiple Myeloma: metabolism
000306240 650_2 $$2MeSH$$aNatural Cytotoxicity Triggering Receptor 2: metabolism
000306240 650_2 $$2MeSH$$aProliferating Cell Nuclear Antigen: metabolism
000306240 7001_ $$aEdri, Avishay$$b1
000306240 7001_ $$aGreenshpan, Yariv$$b2
000306240 7001_ $$aGoldstein, Oron$$b3
000306240 7001_ $$00000-0002-6600-7745$$aOfir, Noa$$b4
000306240 7001_ $$aBolel, Priyanka$$b5
000306240 7001_ $$aAbu Ahmad, Muhammad$$b6
000306240 7001_ $$aZektser, Miri$$b7
000306240 7001_ $$00000-0003-4665-7326$$aCampbell, Kerry S$$b8
000306240 7001_ $$aRouvio, Ory$$b9
000306240 7001_ $$00000-0002-0548-2147$$aGazit, Roi$$b10
000306240 7001_ $$aPorgador, Angel$$b11
000306240 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms23094717$$gVol. 23, no. 9, p. 4717 -$$n9$$p4717$$tInternational journal of molecular sciences$$v23$$x1422-0067$$y2022
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