Van Allen, EliezerGolay, H. G.Liu, YanKoyama, S.Wong, Kwok-KinTaylor-Weiner, AmaroGiannakis, MariosHarden, M.Rojas-Rudilla, V.Chevalier, A.Thai, T.Lydon, C.Mach, S.Wong, J. A.Rabin, A. R.Helmkamp, J.Sholl, LynetteCarter, ScottOxnard, GeoffreyJanne, PasiGetz, GadLindeman, NealHammerman, Peter S.Garraway, LeviHodi, FrankRodig, ScottDranoff, GlennBarbie, David2017-05-182015Van Allen, E. M., H. G. Golay, Y. Liu, S. Koyama, K. Wong, A. Taylor-Weiner, M. Giannakis, et al. 2015. “Long-Term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.” Cancer Immunology Research 3 (8) (May 26): 855–863. doi:10.1158/2326-6066.cir-15-0024.2326-6066http://nrs.harvard.edu/urn-3:HUL.InstRepos:32706163PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer.en-USJournal Article2017-05-1810.1158/2326-6066.CIR-15-0024