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Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression

2014; Cell Press; Volume: 25; Issue: 5 Linguagem: Inglês

10.1016/j.ccr.2014.03.033

1878-3686

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

Cancer Research and Treatments

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.