Chemotherapy induces tumor immune evasion by upregulation of programmed cell death ligand 1 expression in bone marrow stromal cells.
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ABSTRACT: Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations. Mechanistically, chemotherapeutic drugs induce PD-L1 expression in stromal cells through upregulation of granulocyte macrophage colony-stimulating factor and activation of the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Suppression of ERK by a chemical inhibit
SUBMITTER: Yang M
PROVIDER: S-EPMC5527486 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
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