Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNγ That Induce PD-L1 Expression in Head and Neck Cancer
作者： Fernando Concha-Benavente , Raghvendra M Srivastava , Sumita Trivedi , Yu Lei , Uma Chandran
DOI: 10.1158/0008-5472.CAN-15-2001
关键词:
摘要: Many cancer types, including head and neck cancers (HNC), express programmed death ligand 1 (PD-L1). Interaction between PD-L1 its receptor, (PD-1), inhibits the function of activated T cells results in an immunosuppressive microenvironment, but stimuli that induce expression are not well characterized. Interferon gamma (IFNγ) epidermal growth factor receptor (EGFR) utilize Janus kinase 2 (JAK2) as a common signaling node to transmit tumor cell-mediated extrinsic or intrinsic signals, respectively. In this study, we investigated mechanism by which these factors upregulate HNC context JAK/STAT pathway activation, Th1 inflammation, HPV status. We found wild-type, overexpressed EGFR significantly correlated with JAK2 large cohort specimens. Furthermore, was induced EGFR- JAK2/STAT1-dependent manner, specific inhibition prevented upregulation enhanced their immunogenicity. Collectively, our findings suggest novel role for JAK2/STAT1 EGFR-mediated immune evasion, therapies targeting axis may be beneficial block subset tumors.
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