Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression
Author
Xu, Chunxiao
Koyama, Shohei
Zhao, Yanqiu
Chen, Zhao
Akbay, Esra A.
Ji, Hongbin
Watanabe, Hideo
Castrillon, Diego H.
Rustgi, Anil K.
Dranoff, Glenn
Hammerman, Peter S.
Kim, Carla F.
Wong, Kwok-Kin
Hammerman
Published Version
https://doi.org/10.1016/j.ccr.2014.03.033Metadata
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Xu, Chunxiao, Fillmore, Christine M, Koyama, Shohei, Wu, Hongbo, Zhao, Yanqiu, Chen, Zhao, Herter-Sprie, Grit S, Akbay, Esra A, Tchaicha, Jeremy H, Altabef, Abigail, Reibel, Jacob B, Walton, Zandra, Ji, Hongbin, Watanabe, Hideo, Jänne, Pasi A, Castrillon, Diego H, Rustgi, Anil K, Bass, Adam J, Freeman, Gordon J, Padera, Robert F, Dranoff, Glenn, Hammerman, Peter S, Kim, Carla F, and Wong, Kwok-Kin. "Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression." Cancer Cell 25, no. 5 (2014): 590-604.Abstract
Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, gene expression, and microenvironment found in human disease. Lkb1;Pten null (LP) tumors expressed the squamous markers KRT5, p63 and SOX2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. SCA1+NGFR+ fractions were enriched for tumor-propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and NGFR+ cells in human SCCs highly expressed Pd-ligand-1 (PD-L1), suggesting a mechanism of immune escape for TPCs.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369175
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