TY  - EJOU
AU  - YANG, WENZHUO 
AU  - CHEN, HAODONG 
AU  - ZHANG, ZHILAN 
AU  - XIA, ZHIYONG 
AU  - JIN, YUANYUAN 
AU  - YANG, ZHAOYONG 

TI  - Exploring the correlation and mechanism of natural killer cell cytotoxic sensitivity against gastric cancer
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 6
SN  - 1555-3906

AB  -  <b>Background:</b> Human natural killer (NK) cells have attracted widespread attention as a potential adoptive cell therapy (ACT). However, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. There is an urgent need to explore a suitable new treatment plan to overcome weaknesses and support the superior therapeutic activity of NK cells.  <b>Methods:</b> In this study, the mechanisms underlying the susceptibility of gastric cancer (GC) cell lines AGS, HGC-27, and NCI-N87 to NK cell-mediated cytotoxicity were explored.  <b>Results:</b> Lactic dehydrogenase (LDH) release assays showed that all three GC cell lines were susceptible to the umbilical cord blood NK (UCB-NK) cells, and HGC-27 cells with high CD56 expression were the most sensitive to UCB-NK, followed by NCI-N87 and AGS. When the expression of CD56 in HGC-27 cells decreased, the lytic activity of NK cells in HGC-27 cells was abating. In addition, combining oxaliplatin with NK cells produced additive anti-tumor effects <i>in vitro</i>, which may have resulted from oxaliplatin-induced NK group 2 member D (NKG2DL) upregulation in GC cells. These results of cytotoxicity activity showed that inhibition of CD56 expression might suppress the sensitivity of GC cells to NK cell-mediated cytotoxicity, and upregulation of the expression of NKG2DL on the surface of GC cells by oxaliplatin could enhance the killing sensitivity of NK cells.  <b>Conclusion:</b> Collectively, our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC.
KW  - Umbilical cord blood natural killer (UCB-NK) cells; Oxaliplatin; Gastric cancer; Natural killer group 2 member D (NKG2D) ligand (NKG2DL); CD56 (neural cell adhesion molecule NCAM)

DO  - 10.32604/or.2025.059426