RT Journal Article
SR Electronic
T1 Novel, genetically induced mouse model that recapitulates the histological morphology and immunosuppressive tumor microenvironment of metastatic peritoneal carcinomatosis
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000480
DO 10.1136/jitc-2019-000480
VO 8
IS 1
A1 Ssu-Hsueh Tseng
A1 Sung-Taek Park
A1 Brandon Lam
A1 Ya-Chea Tsai
A1 Max A Cheng
A1 Emily Farmer
A1 Deyin Xing
A1 Chien-Fu Hung
YR 2020
UL http://jitc.bmj.com/content/8/1/e000480.abstract
AB Background Peritoneal carcinomatosis is a hallmark of advanced peritoneal tumor progression, particularly for tubal/ovarian high-grade serous carcinomas (HGSCs). Patients with peritoneal carcinomatosis have poor survival rates and are difficult to treat clinically due to widespread tumor dissemination in the peritoneal cavity.Methods We developed a clinically relevant, genetically induced, peritoneal carcinomatosis model that recapitulates the histological morphology and immunosuppressive state of the tumor microenvironment of metastatic peritoneal HGSCs by intraperitoneally injecting shp53, AKT, c-Myc, luciferase and sleeping beauty transposase, followed by electroporation (EP) in the peritoneal cavity of immunocompetent mice (intraperitoneal (IP)/EP mice).Results Similar to the spread of human ovarian cancers, IP/EP mice displayed multiple tumor nodules attached to the surface of the abdomen. Histopathological analysis indicated that these tumors were epithelial in origin. These IP/EP mice also displayed a loss of CD3+ T cell infiltration in tumors, highly expressed inhibitory checkpoint molecules in tumor-infiltrating and global CD4+ and CD8+ T cells, and increased levels of transforming growth factor-β in the ascites, all of which contribute to the promotion of tumor growth.Conclusions Overall, our tumor model recapitulates clinical peritoneal HGSC metastasis, which makes it ideal for preclinical drug screening, testing of immunotherapy-based therapeutics and studying of the tumor biology of peritoneal carcinomatosis.