Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment.

Abstract

Simple SummaryThe mammalian peritoneal cavity harbors the liver, spleen, most of the gastrointestinal tract and other viscera, and is a dynamic microenvironment involved in numerous biological and pathological processes. Here, we present a simple, novel method termed in vivo intraperitoneal lavage (IVIPL) for the minimally invasive monitoring of cells in the peritoneal cavity of mice. IVIPL was used to study changes in the cellular composition of intraperitoneal tumor microenvironments in a syngeneic model of ovarian cancer and a xenograft CAR-T cell-treated ovarian cancer model, validating the application of IVIPL to monitor preclinical intraperitoneal cellular evolution in real time.Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information about future successful clinical treatments. i.p. cellular composition is studied in preclinical models addressing a wide spectrum of other pathophysiological states such as liver cirrhosis, infectious disease, autoimmunity, and aging. The peritoneal cavity is a multifaceted microenvironment that contains various immune cell populations, including T, B, NK, and various myeloid cells, such as macrophages. Analysis of the peritoneal cavity is often obtained by euthanizing mice and performing terminal peritoneal lavage. This procedure inhibits continuous monitoring of the peritoneal cavity in a single mouse and necessitates the usage of more mice to assess the cavity at multiple timepoints, increasing the cost, time, and variability of i.p. studies. Here, we present a simple, novel method termed in vivo intraperitoneal lavage (IVIPL) for the minimally invasive monitoring of cells in the peritoneal cavity of mice. In this proof-of-concept, IVIPL provided real-time insights into the i.p. tumor microenvironment for the development and study of ovarian cancer therapies. Specifically, we studied CAR-T cell therapy in a human high-grade serous ovarian cancer (HGSOC) xenograft mouse model, and we studied the immune composition of the i.p. tumor microenvironment (TME) in a mouse HGSOC syngeneic model.