Inflammatory cues induce expression of immune checkpoint molecule CD137 in breast cancer cells

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FRIEDLOVÁ Nela DÚCKA Monika BENEŠ Petr KNOPFOVÁ Lucia

Rok publikování 2018
Druh Konferenční abstrakty
Citace
Popis CD137 (Tumor Necrosis Factor Receptor Superfamily, Member 9) was originally described as a T cell co-stimulatory molecule. In context of cancer it is a valuable target for immunotherapy, as the agonist CD137 antibodies induce potent T cell-mediated anti-tumor immunity. However, tumor cells utilize CD137-based strategies, such as expression of its soluble variant, in order to prevent co-stimulation of T lymphocytes. Besides, immune checkpoint molecules have been shown to promote the epithelial-mesenchymal transition, the acquisition of tumor-initiating potential and resistance to apoptosis and antitumor drugs, as well as the propensity to disseminate and metastasize. Autocrine and paracrine effects of CD137 receptor/ligand bidirectional signaling in breast cancer are still only marginally understood. We have recently described that CD137 expression is downregulated by metastasis suppressor c-Myb in mammary cancer cells. On contrary, its expression is induced by inflammatory stimuli, such as TNF?. We explore how tumor-derived CD137 affects breast cancer biology and interactions with immune/stromal cells.
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