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Updated: May 9, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Changes in ovarian tumor cell number, tumor vasculature, and T cell function monitored in vivo using a novel
Sandra J Yokota1, John G Facciponte, Raymond J Kelleher
1Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, USA.
Abstract:
Despite an initial response to chemotherapy, most patients with ovarian cancer eventually progress and succumb to their disease. Understanding why effector T cells that are known to infiltrate the tumor do not eradicate the disease after cytoreduction is critically important to the development of novel therapeutic strategies to augment tumor immunity and improve patient outcomes. Such studies have been hampered by the lack of a suitable in vivo model. We report here a simple and reliable model system in which ovarian tumor cell aggregates implanted intraperitoneally into severely immunodeficient NSG mice establish tumor microenvironments within the omentum. The rapid establishment of tumor xenografts within this small anatomically well-defined site enables the recovery, characterization, and quantification of tumor and tumor-associated T cells. We validate here the ability of the omental tumor xenograft (OTX) model to quantify changes in tumor cell number in response to therapy, to quantify changes in the tumor vasculature, and to demonstrate and study the immunosuppressive effects of the tumor microenvironment. Using the OTX model, we show that the tumor-associated T cells originally present within the tumor tissues are anergic and that fully functional autologous T cells injected into tumor-bearing mice localize within the tumor xenograft. The transferred T cells remain functional for up to 3 days within the tumor microenvironment but become unresponsive to activation after 7 days. The OTX model provides for the first time the opportunity to study in vivo the cellular and molecular events contributing to the arrest in T cell function in human ovarian tumors.
Insights
A new ovarian tumor xenograft (OTX) model in mice reveals that T cells infiltrating ovarian tumors become unresponsive. This model helps study why these effector T cells fail to eliminate cancer, aiding new immunotherapy development.
Area of Science:
- Immunology
- Oncology
- Animal Models
Background:
- Ovarian cancer often progresses despite initial chemotherapy response.
- Tumor-infiltrating effector T cells typically fail to eradicate established ovarian tumors.
- Lack of suitable in vivo models hinders understanding of T cell dysfunction in ovarian cancer.
Purpose of the Study:
- To develop and validate a novel in vivo model for studying ovarian cancer and T cell interactions.
- To investigate the reasons for effector T cell unresponsiveness within the ovarian tumor microenvironment.
- To provide a platform for evaluating novel immunotherapeutic strategies.
Main Methods:
- Establishment of ovarian tumor xenografts (OTX) in immunocomdeficient NSG mice.
- Characterization of tumor microenvironment and associated T cells.
- Quantification of tumor cell number and vasculature changes in response to therapy.
- Assessment of T cell function and localization within the OTX model.
Main Results:
- The OTX model reliably establishes human ovarian tumors in the mouse omentum.
- Tumor-associated T cells within the OTX model are anergic (unresponsive).
- Injected autologous T cells localize to the xenograft but lose function within 7 days.
- The model allows quantification of therapeutic responses and study of immunosuppressive microenvironment effects.
Conclusions:
- The OTX model is a valuable tool for studying human ovarian cancer and T cell dysfunction in vivo.
- The tumor microenvironment actively suppresses T cell function, contributing to treatment resistance.
- This model facilitates research into novel immunotherapies to overcome T cell anergy in ovarian cancer.
