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

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.
Yosi Gilad 1 Yossi Eliaz 2 Yang Yu 1 Sang Jun Han 1 Bert W O'Malley 3 David M Lonard 4
Affiliations

Affiliations

  • 1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tx, USA.
  • 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Tx, USA.
  • 3 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tx, USA. [email protected].
  • 4 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tx, USA. [email protected].
Abstract

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.

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