Different Triple-Negative Breast Cancer Tumor Cell Lysates (TCLs) Induce Discrepant Anti-Tumor Immunity by PD1/PDL-1 Interaction.

Abstract

BackgroundTCL-based immunotherapy has been applied in the field cancer therapy. However, it is un clear whether this therapy can be used to treat triple-negative breast cancer (TNBC), and different TNBC cells have distinct responses to this therapy.Material/MethodsIn the present work, we conducted 2 different TCL-based immunotherapies to treat TNBC and compared their anti-tumor effect on 4 TNBC cell lines: MDA-MB-231, MDA-MB-436, HCC1937, and HCC1187.ResultsPeripheral blood mononuclear cells (PBMC) activated by TCL and peripheral blood lymphocytes (PBL) stimulated with TCL-loaded DC demonstrated the ability to kill TNBC cells in vitro, but the killing efficiency of PBL was much higher than that of PBMC. In vivo, PBL stimulated with TCL-loaded DC can also stop the growth of TNBC tumors in mice. HCC1187 and MDA-MD-231 best respond to TCL-based immunotherapy both in vitro and in vivo. The response of HCC1937 was weaker, and that of MDA-MB-436 was lowest among the 4 cell lines. Total mRNA microarray analysis of TNBC cells showed that PDL-1 mRNA expression in HCC1937 and MDA-MD-436 cells was higher than in the other 2 TNBC cell lines, and that of MDA-MB-436 was higher than that of HCC1937. PD1 blocking can decrease the apoptosis rate. These results show that different contents of PDL-1 in TCL, by interacting with PD expression on lymphocytes, can induce different ratios of lymphocyte apoptosis, and then result in distinct response of the 4 TNBC cell lines to TCL-based immunotherapy.ConclusionsTCL-based immunotherapy has discrepant anti-tumor efficiency in different TNBC cell lines by PDL-1/PD interaction, providing the theoretical basis of TCL-based immunotherapy in TNBC.