Human lncRNAs NEAT1 and MALAT1 regulate the tumor microenvironment in lung cancer PDX models in athymic nude mice

We employed PDX models in athymic nude mice to generate lung cancer tumors, aiming to improve early detection and enable personalized treatments. The athymic nude mouse was utilized as the lung cancer PDX model, maintaining the histological and pathological integrity of lung cancer. This model allowed for the analysis of microenvironments through whole transcriptome sequencing to assess gene expression variations across different passages of the PDX model. Candidate genes identified from the RNA-seq analysis were subsequently verified using RT-qPCR. We identified significant changes in genes related to tumor adaptation and immune interactions. Notably, there was a decrease in the expression of Eat-2, Itgb2, Klrd1, and Nkg2d, which are important for NK cell cytotoxic activity. This decrease correlated with the reduction in tumor growth rate from P0 (248 days) to P3 (69 days) to achieve the same tumor volume. Additionally, a decline in the lncRNAs NEAT1 and MALAT1 from PDX passage P0 to P3 was observed and impacting NK cell function and suggesting significant immune system involvement in tumor growth and engraftment. Our findings demonstrate the value of the PDX athymic mice model in lung cancer research. These models are essential for exploring tumor-immune dynamics and developing tailored therapeutic approaches, providing significant insights into tumor behavior and treatment responses.