Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell-of-origin contributes to phenotypic heterogeneity following conditional expression of KrasG12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell type-restricted adenoviral-Cre to target cells expressing Surfactant Protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10+ cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors, and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of proinflammatory and immunomodulatory genes. This is accompanied with an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b+ Gr-1+ tumor-associated neutrophils (TANs) and decreased T-cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.
Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sex, Age, Specimen part
View SamplesWe show that an excess of VEGF-B protects the heart via adaptive cardiac hypertrophy and increased coronary arterial reserve, and by inducing a shift from lipid to glucose metabolism.
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sex, Age, Specimen part
View Samples