Oncology Unit, City Hospital, Faenza, Italy.
Oncology Unit, Macerata Hospital, Macerata, Italy.
Crit Rev Oncol Hematol. 2018 Nov;131:1-6. doi: 10.1016/j.critrevonc.2018.07.008. Epub 2018 Aug 1.
Telomerase activity and telomere length are essential for the pathogenesis of several human diseases, including genitourinary tumors. Telomerase constitutes a complex system that includes human telomerase reverse transcriptase (hTERT), human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1), which are overexpressed in tumor cells compared to normal cells and are involved in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC) and prostate cancer (PCa). In addition, telomerase degraded peptide fragments expressed on the surface of tumor cells lead to their recognition by immune cells. On this scenario, in vitro and in vivo studies have shown effective anti-tumor activity of hTERT-tailored strategies in genitourinary tumors, including active immunotherapy with hTERT-peptide vaccines and passive immunotherapy with hTERT-transduced T cell infusion. This review emphasizes the role of telomerase in the carcinogenesis and progression of genitourinary tumors, thus underlying the potential of emerging telomerase-tailored immunotherapies in these patients.
端粒酶活性和端粒长度对于几种人类疾病的发病机制至关重要，包括泌尿生殖系统肿瘤。端粒酶构成了一个复杂的系统，包括人端粒酶逆转录酶 (hTERT)、人端粒酶 RNA 成分 (hTR) 和端粒酶相关蛋白 1 (TEP1)，与正常细胞相比，肿瘤细胞中端粒酶过度表达，参与肾细胞癌 (RCC)、膀胱癌 (BC) 和前列腺癌 (PCa) 的癌变和进展。此外，肿瘤细胞表面表达的端粒酶降解肽片段导致其被免疫细胞识别。在此背景下，体外和体内研究表明，针对端粒酶的策略在泌尿生殖系统肿瘤中具有有效的抗肿瘤活性，包括 hTERT-肽疫苗的主动免疫治疗和 hTERT 转导 T 细胞输注的被动免疫治疗。本文强调了端粒酶在泌尿生殖系统肿瘤发生和进展中的作用，从而为这些患者新兴的端粒酶定制免疫疗法提供了潜力。
