@Article{or.2025.059426,
AUTHOR = {WENZHUO YANG, HAODONG CHEN, ZHILAN ZHANG, ZHIYONG XIA, YUANYUAN JIN, ZHAOYONG YANG},
TITLE = {Exploring the correlation and mechanism of natural killer cell cytotoxic sensitivity against gastric cancer},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {6},
PAGES = {1485--1494},
URL = {http://www.techscience.com/or/v33n6/61343},
ISSN = {1555-3906},
ABSTRACT = { Background: 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. Methods: 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. Results: 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 in vitro, 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. Conclusion: Collectively, our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC.},
DOI = {10.32604/or.2025.059426}
}