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| Home > Institute Collections > W500 > Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma. |
| Home > Institute Collections > W500 > Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma. |
| Journal Article | DKFZ-2025-02469 |
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2022
Molecular Diversity Preservation International
Basel
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.
Keyword(s): Cell Line, Tumor (MeSH) ; Humans (MeSH) ; Killer Cells, Natural (MeSH) ; Multiple Myeloma: metabolism (MeSH) ; Natural Cytotoxicity Triggering Receptor 2: metabolism (MeSH) ; Proliferating Cell Nuclear Antigen: metabolism (MeSH) ; NKp44 ; PCNA ; clones ; immune check point ; multiple myeloma ; NCR2 protein, human ; Natural Cytotoxicity Triggering Receptor 2 ; PCNA protein, human ; Proliferating Cell Nuclear Antigen
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