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

Med Sci Monit. 2019 Jan 17:25:500-515. doi: 10.12659/MSM.911689.

Abstract

BACKGROUND TCL-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 AND METHODS In 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. RESULTS Peripheral 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. CONCLUSIONS TCL-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.

MeSH terms

  • Animals
  • Apoptosis
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor / metabolism
  • Cell Proliferation
  • Female
  • Humans
  • Immunotherapy
  • Leukocytes, Mononuclear / metabolism
  • Lymphocytes / metabolism
  • Mice
  • Mice, Nude
  • Programmed Cell Death 1 Receptor / metabolism*
  • Signal Transduction
  • Triple Negative Breast Neoplasms / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor