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In vivo Imaging and Therapeutic Treatments in an Orthotopic Mouse Model of Ovarian Cancer
Published on: August 17, 2010
Immune checkpoint inhibitor treatment does not impair ovarian or endocrine function in a mouse model of triple
Payton De La Cruz1,2, Morgan F Woodman-Sousa2,3, Julia N McAdams2
1Brown University, Pathobiology Graduate Program, Providence, RI, 02906.
Background:
Representing 15-20% of all breast cancer cases, triple negative breast cancer (TNBC) is diagnosed more frequently in reproductive-age women and exhibits higher rates of disease metastasis and recurrence when compared with other subtypes. Few targeted treatments exist for TNBC, and many patients experience infertility and endocrine disruption as a result of frontline chemotherapy treatment. While they are a promising option for less toxic therapeutic approaches, little is known about the effects of immune checkpoint inhibitors on reproductive and endocrine function.
Results:
Our findings in a syngeneic TNBC mouse model revealed that therapeutically relevant immunotherapies targeting PD-1, LAG-3, and TIM-3 had no effect on the quality and abundance of ovarian follicles, estrus cyclicity, or hormonal homeostasis. Similarly, in a tumor-free mouse model, we found that ovarian architecture, follicle abundance, estrus cyclicity, and ovulatory efficiency remain unchanged by PD-1 blockade.
Conclusions:
Taken together, our results suggest that immunotherapy may be a promising component of fertility-sparing therapeutic regimens for patients that wish to retain ovarian and endocrine function after cancer treatment.
Insights
Triple negative breast cancer (TNBC) treatments using immunotherapy targeting PD-1, LAG-3, and TIM-3 did not impact ovarian function or hormonal balance in mice. This suggests immunotherapy may support fertility preservation in cancer patients.
Area of Science:
- Oncology
- Reproductive Endocrinology
- Immunology
Background:
- Triple negative breast cancer (TNBC) affects 15-20% of breast cancer patients, disproportionately impacting reproductive-age women.
- TNBC is associated with higher metastasis and recurrence rates, and current treatments often lead to infertility and endocrine disruption.
- The effects of novel immunotherapies, such as immune checkpoint inhibitors, on reproductive and endocrine function remain largely unknown.
Purpose of the Study:
- To investigate the impact of immunotherapies targeting PD-1, LAG-3, and TIM-3 on ovarian function and hormonal homeostasis in a triple negative breast cancer mouse model.
- To assess the effects of PD-1 blockade on ovarian architecture, follicle abundance, estrus cyclicity, and ovulatory efficiency in tumor-free mice.
Main Methods:
- Utilized a syngeneic triple negative breast cancer mouse model to evaluate the effects of multi-target immunotherapies (PD-1, LAG-3, TIM-3).
- Employed a tumor-free mouse model to specifically assess the impact of PD-1 blockade on reproductive parameters.
- Monitored ovarian follicle quality and abundance, estrus cyclicity, and hormonal homeostasis in both models.
Main Results:
- Therapeutic immunotherapies targeting PD-1, LAG-3, and TIM-3 demonstrated no adverse effects on ovarian follicle quality or abundance in the TNBC mouse model.
- Estrus cyclicity and hormonal homeostasis were unaffected by the tested immunotherapies in both TNBC and tumor-free mouse models.
- PD-1 blockade alone did not alter ovarian architecture, follicle abundance, estrus cyclicity, or ovulatory efficiency in tumor-free mice.
Conclusions:
- Immunotherapy targeting PD-1, LAG-3, and TIM-3 appears to preserve ovarian function and hormonal homeostasis.
- These findings suggest that immunotherapy could be a viable component of fertility-sparing treatment strategies for TNBC patients.
- Further research is warranted to confirm the fertility-sparing potential of immunotherapies in clinical settings.
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