Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men.
Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men.
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DOI：
10.1096/fj.202002484r
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Stanton PG
中科院分区：
文献类型：
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作者：
O'Donnell L;Rebourcet D;Dagley LF;Sgaier R;Infusini G;O'Shaughnessy PJ;Chalmel F;Fietz D;Weidner W;Legrand JMD;Hobbs RM;McLachlan RI;Webb AI;Pilatz A;Diemer T;Smith LB;Stanton PG
精子从青春期开始在生精小管中发育，在血睾丸屏障内，以防止它们被免疫系统识别为“非自我”，并且人们普遍认为人类精子特异性蛋白不能进入循环或免疫系统。在癌症中异常表达的精子特异性蛋白质，称为癌症睾丸抗原（CTA），通常被视为癌症生物标志物和治疗靶点，这是基于它们是健康男性循环中不存在的新抗原的假设。在这里，我们确定了广泛的生殖细胞衍生和精子特异性蛋白质，包括多种CTA，这些蛋白质被成年小鼠和人类生精小管的支持细胞选择性地沉积到睾丸间质液（TIF）中，该TIF位于血-睾丸屏障的“外部”。从TIF，蛋白质可以进入循环和免疫系统。精子发生的中断降低了小鼠TIF中这些蛋白的丰度，并且不育男性的TIF中精子特异性CTA显著降低，表明某些CTA对免疫系统的暴露可能取决于生育力状态。这些结果为开发可用于男性不育症管理的血液检测提供了依据，并表明CTA候选人可用于癌症免疫治疗和生物标志物开发，可显示性别特异性和男性生育相关反应。
Sperm develop from puberty in the seminiferous tubules, inside the blood‐testis barrier to prevent their recognition as “non‐self” by the immune system, and it is widely assumed that human sperm‐specific proteins cannot access the circulatory or immune systems. Sperm‐specific proteins aberrantly expressed in cancer, known as cancer‐testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell‐derived and sperm‐specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is “outside” the blood‐testis barrier. From TIF, the proteins can access the circulatory‐ and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm‐specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood‐based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex‐specific and male‐fertility‐related responses.