STAT3 contributes to NK cell recognition by modulating expression of NKG2D ligands in adriamycin-resistant K562/AO2 cells

• Published in: International journal of hematology Vol. 102; no. 5; pp. 536 - 543
• Main Authors: Cai, Xiaohui, Lu, Xuzhang, Jia, Zhuxia, Zhang, Xiuwen, Han, Wenmin, Rong, Xiao, Ma, Lingdi, Zhou, Min, Chen, Baoan
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.11.2015; Springer Nature B.V
• Subjects: Doxorubicin; Drug Resistance, Neoplasm - immunology; Female; Gene Expression Regulation, Leukemic - immunology; Hematology; Humans; K562 Cells; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Leukemia - immunology; Leukemia - pathology; Male; Medicine; Medicine & Public Health; Neoplasm Proteins - immunology; NK Cell Lectin-Like Receptor Subfamily K - immunology; Oncology; Original Article; STAT3 Transcription Factor - immunology; NK cells; K562/AO2; NKG2D ligands; STAT3
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-015-1860-7

Leukemic cells can survive after chemotherapy by acquisition of multidrug resistance genes, but other phenotypes related to escape from immune recognition remain elusive. Adriamycin-resistant K562/AO2 cells are less susceptible to elimination by NK cells compared with wild type K562 cells due to lower expression of NKG2D ligands. Treatment of K562/AO2 cells with STAT3 inhibitor VII resulted in reduced expression of multidrug resistance gene P-glycoprotein, and up-regulation of NKG2D ligands on K562/AO2 cells. Meanwhile, K562/AO2 cells treated with STAT3 inhibitor proliferated less and were more susceptible to killing by NK cells than untreated K562/AO2 cells. The enhanced cytotoxicity of NK cells against K562/AO2 cells was partly blocked by treatment of NK cells with anti-NKG2D antibodies. These data suggest that STAT3 contributes to NK cell recognition by modulating NKG2D ligands in K562/AO2 cells, which may a mechanism by which cells survive and cause relapse of leukemia.