Latvian Biomedical Research and Study Centre, Riga, Latvia.
J Immunother. 2011 Jan;34(1):28-44. doi: 10.1097/CJI.0b013e3181fb64fa.
The identification of novel cancer-related and immunogenic proteins is still a challenge to be faced to improve antigen-specific tumor immunotherapy. The category of so-called cancer-testis (CT) antigens is one of the most perspective groups of proteins for anticancer immune response activation as normally they are expressed in immunoprivileged tissues and are immunogenic if aberrantly generated in tumors. The heterogeneous group of proteins called sperm-associated antigens (SPAG) might encompass novel CT antigens owing to their common expression in male germ cells, their ability to elicit immune response underlying infertility, and lately proposed oncogenic properties. We carried out a comprehensive analysis of the expression pattern in various normal and cancerous tissues and assessed the frequency of spontaneous humoral immune response against members of the SPAG group in cancer patients using phage-displayed antigen microarrays. Our results show that out of 15 analyzed SPAG genes only SPAG1, SPAG6, SPAG8, SPAG15, and SPAG17 are predominantly expressed in testis, whereas the others are ubiquitously expressed with only a testis-associated alternative splice variant of SPAG16. mRNA expression of SPAG1, SPAG6, and alternative splice variants of SPAG8, SPAG16, and SPAG17 was elevated in various tumors with frequencies ranging from approximately 10% to 70%. The upregulation of SPAG6 in lung and breast cancer was confirmed by immunohistochemical analysis of tumor and normal tissue microarrays. Cancer-associated spontaneous humoral immune response was detected against SPAG1, SPAG6, SPAG8, and a novel testis-specific splice variant of SPAG17 and ascribe these as novel CT antigens that potentially are applicable as immunotherapeutic targets and serologic biomarkers.
鉴定新型癌症相关和免疫原性蛋白仍然是一个挑战，需要提高抗原特异性肿瘤免疫治疗。所谓的癌症睾丸（CT）抗原类别是激活抗肿瘤免疫反应的最有前景的蛋白组之一，因为它们通常在免疫豁免组织中表达，如果在肿瘤中异常产生，则具有免疫原性。所谓的精子相关抗原（SPAG）蛋白组是一组异质蛋白，由于它们在男性生殖细胞中的共同表达、引起不育的免疫反应能力，以及最近提出的致癌特性，可能包含新型 CT 抗原。我们对各种正常和癌组织中的表达模式进行了全面分析，并使用噬菌体展示抗原微阵列评估了癌症患者中针对 SPAG 组成员的自发体液免疫反应的频率。我们的结果表明，在分析的 15 个 SPAG 基因中，只有 SPAG1、SPAG6、SPAG8、SPAG15 和 SPAG17 主要在睾丸中表达，而其他基因则广泛表达，只有 SPAG16 具有睾丸相关的替代剪接变体。SPAG1、SPAG6 和替代剪接变体 SPAG8、SPAG16 和 SPAG17 的 mRNA 表达在各种肿瘤中升高，频率约为 10%至 70%。SPAG6 在肺癌和乳腺癌中的上调通过肿瘤和正常组织微阵列的免疫组织化学分析得到证实。针对 SPAG1、SPAG6、SPAG8 和 SPAG17 的新型睾丸特异性剪接变体检测到与癌症相关的自发体液免疫反应，并将其归为新型 CT 抗原，这些抗原可能适用于免疫治疗靶点和血清学生物标志物。
