Loss of lkb1 and pten leads to lung squamous cell carcinoma with elevated pd-l1 expression

Chunxiao Xu, Christine M. Fillmore, Shohei Koyama, Hongbo Wu, Yanqiu Zhao, Zhao Chen, Grit S. Herter-Sprie, Esra A. Akbay, Jeremy H. Tchaicha, Abigail Altabef, Jacob B. Reibel, Zandra Walton, Hongbin Ji, Hideo Watanabe, Pasi A. Jänne, Diego H. Castrillon, Anil K. Rustgi, Adam J. Bass, Gordon J. Freeman, Robert F. PaderaGlenn Dranoff, Peter S. Hammerman, Carla F. Kim, Kwok Kin Wong

Research output: Contribution to journalArticle

223 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)590-604
Number of pages15
JournalCancer Cell
Volume25
Issue number5
DOIs
StatePublished - May 12 2014

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Xu, C., Fillmore, C. M., Koyama, S., Wu, H., Zhao, Y., Chen, Z., Herter-Sprie, G. S., Akbay, E. A., Tchaicha, J. H., Altabef, A., Reibel, J. B., Walton, Z., Ji, H., Watanabe, H., Jänne, P. A., Castrillon, D. H., Rustgi, A. K., Bass, A. J., Freeman, G. J., ... Wong, K. K. (2014). Loss of lkb1 and pten leads to lung squamous cell carcinoma with elevated pd-l1 expression. Cancer Cell, 25(5), 590-604. https://doi.org/10.1016/j.ccr.2014.03.033