Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation
Golay, H. G.
Wong, J. A.
Rabin, A. R.
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CitationVan 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.
AbstractPD-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.
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