Tumor characteristics associated with engraftment of patient‐derived non–small cell lung cancer xenografts in immunocompromised mice

Abstract

Patient-derived xenograft (PDX) models are increasingly used in translational research, however, the engraftment rates of patient tumor samples in immunodeficient mice to PDX models vary greatly. Tumor tissue samples from 308 NSCLC patients were implanted in immunodeficient mice. The patients were followed for 1.5 to about 6 years. We performed histological analysis of PDXs and some residual tumor tissues in mice with failed PDX growth at 1 year after implantation. Quantitative PCR and ELISA were performed to measure the levels of Epstein-Barr virus genes and human immunoglobulin G in PDX samples. Patients’ characteristics were compared for PDX growth and overall survival as outcomes using cox regression analyses. Overall engraftment rate of NSCLC PDXs was 34%. Squamous cell carcinomas had a higher engraftment rate (53%) than did adenocarcinomas. Tumor samples from patients with stage II and III diseases and from larger tumors had relatively high engraftment rates. Patients whose tumors successfully engrafted had worse overall survival, particularly those with adenocarcinoma, stage III or IV disease, and moderately differentiated tumors. Lymphoma formation was one of factors associated with engraftment failures. Human CD8+ and CD20+ cells were detected in residual samples of tumor tissue that failed to generate a PDX at 1 year after implantation. Human immunoglobulin G was detected in the plasma of mice that did not have PDX growth at 14 months after implantation. Our results indicate that characteristics of cancer cells and tumor immune microenvironment in primary tumors can both affect engraftment of a primary tumor sample. This study identified clinical tumor characteristics, biological features of cancer cells, and tumor immune microenvironment are associated with successful engraftment of tumor samples. Patients’ immune cells can be present for a long time in residual tissue from failed PDXs, which indicates that these immune cells may play roles in inhibiting PDX engraftment.