Rohozinski Jan, Edwards Creighton L
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United States.
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States.
Front Oncol. 2020 Nov 30;10:590408. doi: 10.3389/fonc.2020.590408. eCollection 2020.
Cancer/Testis (C/T) antigens are a group of antigens, expressed in almost all types of cancers, which can elicit an immune response in patients whose cancers express these antigens. They are currently of great interest as targets for the development of cancer biomarkers and the creation of immunotherapies that directly target tumors in patients. Currently there are 280 C/T antigens and their variants listed on the C/T antigen data base. All known C/T antigens are encoded for by genes which are normally only expressed in the male testis; specifically during the process of spermatogenesis. They are therefore only expressed in germ cells that are in the process of differentiating into sperm. Expression of C/T antigens in tumors is thus a biological anomaly as, with the exception of germ cell tumors, cancers arise from somatic tissues which are not known to express any of the genes specifically involved in spermatogenesis. How and why C/T antigens are expressed in tumors remains an enigma. In this paper we present a hypothesis which proposes a mechanism for the activation of C/T antigen encoding genes in tumors. We propose that aberrant activation of the human autosomal retrogene, , which regulates initiation and maintenance of spermatogenesis in males, is responsible for C/T expression. Because both male and females have tumors that express C/T antigens activation of spermatogenesis genes in tumors must involve a non-sex specific pathway. This can be explained by the copy number of genes uniquely present within the human genome.
癌/睾丸（C/T）抗原是一类在几乎所有类型癌症中都有表达的抗原，在表达这些抗原的癌症患者体内可引发免疫反应。作为癌症生物标志物开发的靶点以及针对患者肿瘤的免疫疗法的创建靶点，它们目前备受关注。目前，C/T抗原数据库中列出了280种C/T抗原及其变体。所有已知的C/T抗原均由通常仅在男性睾丸中表达的基因编码；具体而言是在精子发生过程中表达。因此，它们仅在正分化为精子的生殖细胞中表达。C/T抗原在肿瘤中的表达因此是一种生物学异常现象，因为除生殖细胞肿瘤外，癌症源自体细胞组织，而这些体细胞组织并不表达任何与精子发生特别相关的基因。C/T抗原如何以及为何在肿瘤中表达仍是一个谜。在本文中，我们提出一种假说，该假说提出了肿瘤中C/T抗原编码基因激活的机制。我们认为，调节男性精子发生起始和维持的人类常染色体反转录基因的异常激活是C/T表达的原因。由于男性和女性都有表达C/T抗原的肿瘤，肿瘤中精子发生基因的激活必定涉及一条非性别特异性途径。这可以通过人类基因组中独特存在的基因拷贝数来解释。
