CD56 does not contribute to the anti-tumor, tissue homing, and glycolytic capacity of human NK cells.

Autor: Portillo AL; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Rojas EA; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada., Mehboob M; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Moinuddin A; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Balint E; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Feng E; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Silvestri C; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Vahedi F; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Ritchie TM; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada., Mansour AJ; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Bramson JL; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada., Ashkar AA; Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada.; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON L8S 4M1, Canada.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1093/jleuko/qiae227
Abstrakt: Natural Killer (NK) cells are critical innate immune cells involved in the clearance of virally infected and malignant cells. Human NK cells are distinguished by their surface expression of CD56 and a lack of CD3. While CD56 expression and cell surface density has long been used as the prototypic marker to characterize primary human NK cell functional subsets, the exact functional role of CD56 in primary human NK cells is still not fully understood. Here we eliminated the expression of CD56 in human ex vivo expanded NK cells (CD56bright) using CRISPR/Cas9 in order to assess the function of CD56 in this highly activated and cytotoxic NK cell population. We show that the expression of CD56 has no effect on NK cell proliferative capacity or expression of various activation and inhibitory markers. Further, CD56 does not contribute to NK cell-mediated cytotoxicity, inflammatory cytokine production, or the ability of NK cells to control tumor engraftment in vivo. We also found that while deletion of CD56 did not impact NK cell glycolytic metabolism it did increase NK cell reliance on oxidative phosphorylation. Lastly, CD56 does not alter expanded NK cell in vivo tissue trafficking. Our results indicate that while CD56 expression could be used to indicate a hyper-functional state of NK cells, it does not directly influence the anti-tumor functions of expanded NK cells.
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Databáze: MEDLINE