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Characterization of an orthotopic mouse transplant model reveals early changes in the tumor microenvironment of lung cancer
Minsu Na 1,2 (Graduate student), Huiram Kang 1,2 (Graduate student), Nayoung Kim 1,2 (Postdoctoral researcher), Areum Jo 1,2 (Research worker), Hae-Ock Lee 1,2,* (Professor)
1Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Korea,
2Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, 06591, Korea
Abstract
To understand the cellular and molecular dynamics in the early stages of lung cancer, we explored a mouse model of orthotopic tumor transplant created from the Lewis Lung Carcinoma (LLC) cell line. Employing single-cell RNA sequencing, we analyzed the cellular landscape during tumor engraftment, focusing particularly on LLC cells harboring the Kras G12C mutation. This allowed us to identify LLC tumor cells via the detection of mutant Kras transcripts and observe elevated levels of Myc and mesenchymal gene expression. Moreover, our study revealed significant alterations in the lung microenvironment, including the activation of tissue remodeling genes in a fibroblast and the downregulation of MHC class II genes in myeloid subsets. Additionally, T/NK cell subsets displayed more regulatory phenotypes, coupled with reduced proliferation in CD8+ T cells. Collectively, these findings enhance our understanding of lung cancer progression, particularly in a tumor microenvironment with low immunogenicity.
Abstract, Accepted Manuscript [Submitted on January 20, 2024, Accepted on March 23, 2024]
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