NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment

Author:

Li Fengqi12ORCID,Wang Zhongyi12,Zheng Dongpeng12,Pang Zhaojun12,Feng Chunjing23,Ma Yue23,Yang Ce12,Li Xueren4,Peng Shouchun45,Liu Zichuan124,Mu Xin124ORCID

Affiliation:

1. School of Pharmaceutical Science and Technology, Tianjin University Tianjin China

2. Tianjin University and Health‐Biotech United Group Joint Laboratory of Innovative Drug Development and Translational Medicine Tianjin University Tianjin China

3. Health‐Biotech Group Stem Cell Research Institute Tianjin China

4. Jinnan Hospital, Tianjin University (Tianjin Jinnan Hospital) Tianjin China

5. Academy of Medical Engineering and Translational Medicine Tianjin University Tianjin China

Abstract

AbstractNatural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well‐defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)‐NK cells. By co‐culturing NK cells with dasatinib to test the cell counts and target cell‐killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB‐NK‐killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB‐NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

Funder

Tianjin Municipal Science and Technology Bureau

Publisher

Wiley

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