학술논문
Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation
Document Type
Journal Article
Author
Van Allen, Eliezer Mendel; Golay, H. G.; Liu, Yan; Koyama, S.; Wong, Kwok-Kin; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, M.; Rojas-Rudilla, V.; Chevalier, A.; Thai, T.; Lydon, C.; Mach, S.; Wong, J. A.; Rabin, A. R.; Helmkamp, J.; Sholl, Lynette Marie; Carter, Scott Lambert; Oxnard, Geoffrey Raymond; Janne, Pasi Antero; Getz, Gad A; Lindeman, Neal I.; Hammerman, Peter Seth; Garraway, Levi Alexander; Hodi, Frank Stephen; Rodig, Scott J.; Dranoff, G; Barbie, David Allen
Source
Van 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.
Subject
Language
English
ISSN
2326-6066
Abstract
PD-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.