Dunn Zachary Spencer, Li Yan-Ruide, Yu Yanqi, Lee Derek, Gibbons Alicia, Kim James Joon, Zhou Tian Yang, Li Mulin, Nguyen Mya, Cen Xinjian, Zhou Yang, Wang Pin, Yang Lili
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Cancers (Basel). 2022 Mar 31;14(7):1775. doi: 10.3390/cancers14071775.
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.
小鼠腹腔内（i.p.）实验模型可以重现腹腔内癌症的播散过程，并可能有助于揭示未来成功临床治疗的关键信息。在解决诸如肝硬化、传染病、自身免疫和衰老等广泛其他病理生理状态的临床前模型中，对腹腔内细胞组成进行了研究。腹腔是一个多方面的微环境，包含各种免疫细胞群体，包括T细胞、B细胞、NK细胞以及各种髓样细胞，如巨噬细胞。对腹腔的分析通常通过对小鼠实施安乐死并进行终末期腹腔灌洗来获得。该操作阻碍了对单个小鼠腹腔的连续监测，并且需要使用更多小鼠来在多个时间点评估腹腔，从而增加了腹腔内研究的成本、时间和变异性。在此，我们提出一种简单、新颖的方法，称为体内腹腔灌洗（IVIPL），用于对小鼠腹腔内细胞进行微创监测。在这个概念验证中，IVIPL为卵巢癌治疗的开发和研究提供了对腹腔肿瘤微环境的实时洞察。具体而言，我们在人高级别浆液性卵巢癌（HGSOC）异种移植小鼠模型中研究了CAR-T细胞疗法，并在小鼠HGSOC同基因模型中研究了腹腔肿瘤微环境（TME）的免疫组成。
