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Killing efficiency affected by muturally modulated PD-1 and PD-L1 expression via NKT-hepatoma cell intereations
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  • Liwei Liu ,
  • Mingya Yang,
  • Qia Xu ,
  • Yide Qin,
  • Bo Liu,
  • Min Zhou,
  • Yan Cheng ,
  • Heming Xu
Liwei Liu
Anhui Medical University
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Mingya Yang
 First Affiliated Hospital of Anhui Medical University
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Qia Xu
Anhui Medical University,
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Yide Qin
Anhui Medical University
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Bo Liu
The PLA Clinical College(901 Hospital) of Anhui Medical University
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Min Zhou
Anhui Kedgene Science and Technology Co. Ltd
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Yan Cheng
The PLA Clinical College(901 Hospital) of Anhui Medical University
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Heming Xu
The PLA Clinical College(901 Hospital) of Anhui Medical University
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Abstract

Tumour antigens and other lymphocyte-activating factors, such as IFN-γ, can induce PD-1 expression, The combination of PD-1 with PD-L1 has negative effects on activation, proliferation and cytotoxicity of T lymphocytes. The use of a PD-1/PD-L1 blocking strategy has produced some achievements in solid tumours. The immune checkpoints related to blocking therapy ultimately depend on T cells to express an effect. It is unclear Whether interaction between T cells and hepatoma cells on different backgrounds affects PD1 or PDL1 expression,It is also unclear whether there is a difference between the killing effect of knocking out PD-1 receptors and that of blocking the PD-1 pathway with monoclonal antibodies on hepatoma cells with different backgrounds . In this study, the interactions between expression of PD-1/PD-L1 were observed by coculturing umbilical cord blood derived NKT cells with hepatoma cell lines on different backgrounds (MHCC97H,HepG2, SMMC-7721 and Huh-7), Furthermore, the killing effect of NKT cells targeting tumor cells were investigated after knocking out PD-1 on NKT cells or applying monoclonal antibodies to block PD-1. Our results showed that Coculture of hepatoma cells with NKT cells mutually affected the expression of PD-L1 and PD-1;Hepatoma cells in different genetic lines respond to NKT-cell-induced PD-L1 stimulats differently, and those tumor cells with lower PDL1 expression fail to PD1 blocking intervention; The killing effect was more time-efficient with PD-1 knockout than with monoclonal antibody blockade, although it only advanced one or two weeks.