Effects of PD-1 blockade on ovarian follicles in a prepubertal female mouse.
Effects of PD-1 blockade on ovarian follicles in a prepubertal female mouse.
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DOI：
10.1530/joe-21-0209
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发表时间：
2021-11-24
期刊：
影响因子：
--
通讯作者：
Kim SY
中科院分区：
文献类型：
--
作者：
Xu PC;Luan Y;Yu SY;Xu J;Coulter DW;Kim SY
免疫疗法已经出现在癌症治疗的前沿。检查点抑制剂pembrolizumab （KEYTRUDA）是一种靶向程序性细胞死亡蛋白1 （PD-1）的嵌合抗体，已被FDA批准用于复发或难治性经典霍奇金淋巴瘤的儿科患者。然而，目前尚无关于派姆单抗对女性儿科患者卵巢影响的已发表数据。在本研究中，给青春期前免疫正常和免疫缺陷的雌性小鼠注射派姆单抗或抗小鼠PD-1抗体。在免疫功能正常的小鼠中，注射派姆单抗和抗小鼠PD-1抗体后，原始卵泡数量显著减少。然而，在免疫缺陷裸鼠中未观察到卵泡数量的变化。超排卵试验和阴道口实验表明，对照组和抗小鼠PD-1抗体治疗组在COCs数量和青春期开始时间上没有差异，表明对短期生育能力没有影响。促炎细胞因子TNF-α在卵巢中随COX-2上调而升高。小鼠经抗小鼠PD-1抗体处理后，部分卵巢卵泡内及卵巢间质细胞间可见CD3+ t细胞浸润。因此，PD-1免疫检查点阻断可能通过CD3+ t细胞浸润后的炎症机制影响卵巢储备。
Immunotherapy has emerged at the forefront of cancer treatment. Checkpoint inhibitor pembrolizumab (KEYTRUDA), a chimeric antibody which targets programmed cell death protein 1 (PD-1), has been approved by the FDA for use in pediatric patients with relapsed or refractory classical Hodgkin’s lymphoma. However, there is currently no published data regarding the effects of pembrolizumab on the ovary of female pediatric patients. In this study, prepubertal immunocompetent and immunodeficient female mice were injected with pembrolizumab or anti-mouse PD-1 antibody. The number of primordial follicles significantly decreased post-injection of both pembrolizumab and anti-mouse PD-1 antibody in immunocompetent mice. However, no changes in follicle numbers were observed in immunodeficient nude mice. Superovulation test and vaginal opening experiments suggest that there is no difference in the number of COCs and the timing of puberty onset between the control and anti-mouse PD-1 antibody treatment groups, indicating that there is no effect on short-term fertility. Elevation of pro-inflammatory cytokine TNF-α following COX-2 upregulation was observed in the ovary. CD3+ T-cell infiltration was detected within some ovarian follicles and between stromal cells of the ovaries in mice following treatment with anti-mouse PD-1 antibody. Thus, PD-1 immune checkpoint blockade affects the ovarian reserve through a mechanism possibly involving inflammation following CD3+ T-cell infiltration.
影响因子：
4.7
作者：
Gopalakrishnan D;Jain RK;Herbst L;Sikorski M;Mandava S;Azabdaftari G;Xu B;LeVea C;Robillard K;Ernstoff MS;George S
通讯作者：
George S