Scientific Publications

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

Publication TypeJournal Article
AuthorsXu, C., Fillmore CM, Koyama S., Wu H., Zhao Y., Chen Z., Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A., Reibel JB, Walton Z., Ji H., Watanabe H., Jänne PA, Castrillon DH, Rustgi AK, Bass AJ, Freeman GJ, Padera RF, Dranoff G., Hammerman PS, Kim CF, and Wong KK
AbstractLung 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.
Year of Publication2014
JournalCancer cell
Volume25
Issue5
Pages590-604
Date Published (YYYY/MM/DD)2014/05/12
ISSN Number1535-6108
DOI10.1016/j.ccr.2014.03.033
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24794706?dopt=Abstract