You are here

Cancer Cell DOI:10.1016/j.ccr.2014.03.033

Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.

Publication TypeJournal Article
Year of Publication2014
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, Wong, K-K
JournalCancer Cell
Volume25
Issue5
Pages590-604
Date Published2014 May 12
ISSN1878-3686
KeywordsAnimals, Antigens, CD274, Antigens, Ly, B-Lymphocytes, Carcinoma, Squamous Cell, Disease Models, Animal, Immune Tolerance, Keratin-15, Keratin-5, Killer Cells, Natural, Lung, Lung Neoplasms, Lymphocyte Activation, Macrophages, Membrane Proteins, Metabolome, Mice, Neutrophils, Phosphoproteins, Protein-Serine-Threonine Kinases, PTEN Phosphohydrolase, Receptor, Nerve Growth Factor, SOXB1 Transcription Factors, T-Lymphocytes, Trans-Activators, Transcription, Genetic, Tumor Cells, Cultured, Tumor Escape
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1535-6108(14)00133-0
DOI10.1016/j.ccr.2014.03.033
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24794706?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID24794706
PubMed Central IDPMC4112370
Grant ListCA143083 / CA / NCI NIH HHS / United States
CA166480 / CA / NCI NIH HHS / United States
R01 CA122794 / CA / NCI NIH HHS / United States
HL100402 / HL / NHLBI NIH HHS / United States
K08 CA163677 / CA / NCI NIH HHS / United States
R01 CA137181 / CA / NCI NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
CA137181 / CA / NCI NIH HHS / United States
U01 HL100402 / HL / NHLBI NIH HHS / United States
CA163896 / CA / NCI NIH HHS / United States
P01 CA154303 / CA / NCI NIH HHS / United States
R01 CA163896 / CA / NCI NIH HHS / United States
R01 CA166480 / CA / NCI NIH HHS / United States
HL090136 / HL / NHLBI NIH HHS / United States
CA122794 / CA / NCI NIH HHS / United States
P01 CA098101 / CA / NCI NIH HHS / United States
R01 CA140594 / CA / NCI NIH HHS / United States
CA140594 / CA / NCI NIH HHS / United States
P0CA154303 / CA / NCI NIH HHS / United States
R01 HL090136 / HL / NHLBI NIH HHS / United States
P0CA120964 / CA / NCI NIH HHS / United States
R01 CA143083 / CA / NCI NIH HHS / United States
CA163677 / CA / NCI NIH HHS / United States
CA141576 / CA / NCI NIH HHS / United States
U01 CA141576 / CA / NCI NIH HHS / United States
CA098101 / CA / NCI NIH HHS / United States