Killing efficiency affected by muturally modulated PD-1 and PD-L1
expression via NKT-hepatoma cell intereations
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.