Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA.
University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH.
JCO Oncol Pract. 2022 Dec;18(12):815-822. doi: 10.1200/OP.22.00469. Epub 2022 Sep 29.
Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti-PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.
免疫检查点抑制已在多种癌症类型中取得显著疗效，包括黑色素瘤。黑色素瘤是生殖年龄段人群中第二常见的癌症，但辅助治疗和一线免疫疗法的生殖毒性在很大程度上尚不清楚。正常的先天和适应性免疫系统在男性和女性生殖器官的稳态中起着至关重要的作用，对于着床、生育和成功妊娠也是必不可少的。细胞程序性死亡受体 1/细胞程序性死亡配体 1（PD-1/PD-L1）通路在生育和妊娠的几个方面都起着至关重要的作用。最近的研究主要集中在 PD-1/PD-L1 通路在胎母耐受中的作用，强调了完整的免疫调节在促进成功妊娠中的重要性。在这篇综述中，我们描述了一名生殖年龄段女性 IIIC 期黑色素瘤患者在接受 pembrolizumab 治疗后寻求生育指导的案例。我们讨论了免疫检查点抑制剂已知的与生育相关的毒性，以及男性和非妊娠女性中潜在的生殖毒性靶点，以及抗 PD-1 治疗与胎母耐受的关系。知情决策将受益于数据和共识。
