PT  - JOURNAL ARTICLE
AU  - Ssu-Hsueh Tseng
AU  - Sung-Taek Park
AU  - Brandon Lam
AU  - Ya-Chea Tsai
AU  - Max A Cheng
AU  - Emily Farmer
AU  - Deyin Xing
AU  - Chien-Fu Hung
TI  - Novel, genetically induced mouse model that recapitulates the histological morphology and immunosuppressive tumor microenvironment of metastatic peritoneal carcinomatosis
AID  - 10.1136/jitc-2019-000480
DP  - 2020 Feb 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e000480
VI  - 8
IP  - 1
4099  - http://jitc.bmj.com/content/8/1/e000480.short
4100  - http://jitc.bmj.com/content/8/1/e000480.full
SO  - J Immunother Cancer2020 Feb 01; 8
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.