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 journalArticlepeer-review

323 Scopus citations


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
Pages (from-to)590-604
Number of pages15
JournalCancer Cell
Issue number5
StatePublished - May 12 2014

Bibliographical note

Funding Information:
We thank the Boston Children’s Hospital flow cytometry facility and members of the C.F.K. and Zon Labs for helpful discussions. This work was supported in part by the United Against Lung Cancer and the Susan Spooner Research Fund (to K.-K.W.); American Cancer Society Post-Doctoral Fellowship PF-12-151-01-DMC (to C.M.F.); a Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award (to S.K.); American Cancer Society Research Scholar grant RSG-08-082-01-MGO, the V Foundation for Cancer Research, a Basil O’Conner March of Dimes Starter Award, the Harvard Stem Cell Institute, and the Lung Cancer Research Foundation (to C.F.K.); the Cancer Prevention Research Institute of Texas (RP100550); and grants HL090136, HL100402, CA122794, CA140594, CA163896, CA166480, P0CA154303, CA098101, CA141576, CA137181, P0CA120964, CA143083, and CA163677 from the NIH.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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