De La Cruz Payton, Woodman-Sousa Morgan F, McAdams Julia N, Sweeney Ellia, Hakim Lola, Morales Aquino Melanie, Grive Kathryn J
Brown University, Pathobiology Graduate Program, Providence, RI, 02906.
Women and Infants Hospital of Rhode Island, Department of Obstetrics and Gynecology, Program in Women's Oncology, Providence, RI 02905.
bioRxiv. 2024 Aug 19:2024.08.14.607933. doi: 10.1101/2024.08.14.607933.
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.
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.
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.
三阴性乳腺癌(TNBC)占所有乳腺癌病例的15%-20%,在育龄妇女中诊断更为频繁,与其他亚型相比,其疾病转移和复发率更高。TNBC的靶向治疗方法很少,许多患者因一线化疗而出现不孕和内分泌紊乱。虽然免疫检查点抑制剂是毒性较小的治疗方法的一个有前景的选择,但关于其对生殖和内分泌功能的影响知之甚少。
我们在同基因TNBC小鼠模型中的研究结果表明,针对PD-1、LAG-3和TIM-3的具有治疗相关性的免疫疗法对卵巢卵泡的质量和数量、发情周期或激素稳态没有影响。同样,在无肿瘤小鼠模型中,我们发现PD-1阻断对卵巢结构、卵泡数量、发情周期和排卵效率没有影响。
综上所述,我们的结果表明,免疫疗法可能是希望在癌症治疗后保留卵巢和内分泌功能的患者保留生育能力治疗方案的一个有前景的组成部分。