Drug-induced PD-L1 expression and cell stress response in breast cancer cells can be balanced by drug combination

Sci Rep. 2019 Oct 22;9(1):15099. doi: 10.1038/s41598-019-51537-7.


The impact of chemotherapy on tumor-immune system interaction can be either beneficial or harmful, which is represented by the immunogenic cell death (ICD) paradigm or overexpression of the immunosuppressive protein - programmed death ligand 1 (PD-L1). In this study we explore the impact of steroid receptor coactivator inhibitor, other targeted anti-cancer compounds and traditional chemotherapeutic agents on the expression of PD-L1 in four breast cancer (BC) cell lines. Our results show that these agents induce PD-L1 expression, yet the magnitude of this induction varies substantially across the different compounds. In addition, we utilized the E0771 ER + BC cells as a model to examine in greater detail the relationship between pharmacological pressure, cell stress and the induction of PD-L1. Our results imply that drug induced PD-L1 expression occurs in the broader context of cell-stress, without conferring acquired drug-resistance. Furthermore, a balance between BC cytotoxicity, induction of cell-stress and the overexpression of PD-L1 can be achieved through the selection of appropriate combinations of anti-cancer compounds. Therefore, we propose that drug combination can be employed not only for increasing the direct kill of cancer cells, but also as a strategy to minimize the activation of immunosuppressive and cancer cell pro-survival program responses during drug treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Mice
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Stress, Physiological*
  • Triple Negative Breast Neoplasms / metabolism*


  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Receptors, Estrogen