Lkb1 和 Pten 的缺失导致肺鳞状细胞癌，并伴有 PD-L1 表达升高。
Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.
机构信息
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2014 May 12;25(5):590-604. doi: 10.1016/j.ccr.2014.03.033. Epub 2014 May 1.
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.
肺鳞状细胞癌（SCC）是一种致命的疾病，目前的治疗方法还不够完善。我们证明，在小鼠肺部中 Lkb1 和 Pten 的双等位基因失活会导致 SCC，其重现了在人类疾病中发现的组织学、基因表达和微环境。Lkb1;Pten 缺失（LP）肿瘤表达鳞状标记物 KRT5、p63 和 SOX2，并且在转录上类似于人类 SCC 的基底亚型。与小鼠腺癌不同，LP 肿瘤中富含富含肿瘤相关中性粒细胞的免疫群体。SCA1(+)NGFR(+) 分数富含能够在原位测定中连续移植疾病的肿瘤起始细胞（TPCs）。LP 模型中的 TPCs 和人类 SCC 中的 NGFR(+) 细胞高度表达 PD-配体-1（PD-L1），这表明 TPCs 免疫逃逸的一种机制。
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