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Authors demostrate that EGFR induces HLA class I downregulation via SHP2-STAT1 suppression, EGFR blockade with cetuximab induced upregulation of IFNγ receptor, STAT1 activation and upregulation of HLA-B/C alleles more than HLA-A alleles. HLA class I upregulation was significantly associated with clincal response to cetuximab in a single agent neo-adjuvant phase II clinical trial.
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34 Topalian, S.L., Hodi, F.S., Brahmer, J.R., Gettinger, S.N., Smith, D.C., McDermott, D.F., Powderly, J.D., Carvajal, R.D., Sosman, J.A., Atkins, M.B., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366 (2012), 2443–2454.
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37 Akbay, E.A., Koyama, S., Carretero, J., Altabef, A., Tchaicha, J.H., Christensen, C.L., Mikse, O.R., Cherniack, A.D., Beauchamp, E.M., Pugh, T.J., et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3 (2013), 1355–1363.
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38
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Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNgamma that induce PD-L1 expression in head and neck cancer
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