Characterization of tumor microenvironment using single cell RNA sequencing in Lewis Lung Carcinoma cell transplantation mouse model
The tumor microenvironment holds significant importance in cancer development and progression. Research conducted using mouse models of tumor cell transplantation can enhance our comprehension of the tissue microenvironment that allows tumor growth at an early stage. Among these models, those featuring the Lewis Lung Carcinoma (LLC) cell line are noteworthy due to their low immunogenic features. Since numerous cancer patients do not respond effectively to current immunotherapy, it is imperative to investigate models with low immunogenic features. Consequently, this study employed single-cell RNA sequencing on an orthotopic lung cancer mouse model utilizing the LLC cell line to profile the characteristics of diverse cell types that emerge in the lung during tumor engraftment. The lung microenvironment exhibited discernible transformations, including fibrogenic gene expression, increased cell-to-cell and cell-to-extracellular matrix adhesion, and reduced infiltration of T cells compared to lungs without tumor engraftment. In conclusion, these findings reveal cellular and molecular alterations that can be targeted for tumor prevention and treatment for low-immunogenic tumors. Overall design: Eight to nine-week-old week old female C57BL/6 mice were intracardially injected with 1 x 104-1 x 105  LL/2-Luc2 cells. The mice were sacrificed on days 19 to 24 after tumor injection. Tissue specimens were analyzed by H&E staining, scRNAseq(10x genemics).