Negrini Simone, De Palma Raffaele, Filaci Gilberto
Internal Medicine, Clinical Immunology and Translational Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
Cancers (Basel). 2020 Aug 12;12(8):2260. doi: 10.3390/cancers12082260.
Telomerase is a reverse transcriptase that maintains telomeres length, compensating for the attrition of chromosomal ends that occurs during each replication cycle. Telomerase is expressed in germ cells and stem cells, whereas it is virtually undetectable in adult somatic cells. On the other hand, telomerase is broadly expressed in the majority of human tumors playing a crucial role in the replicative behavior and immortality of cancer cells. Several studies have demonstrated that telomerase-derived peptides are able to bind to HLA (human leukocyte antigen) class I and class II molecules and effectively activate both CD8 and CD4 T cells subsets. Due to its broad and selective expression in cancer cells and its significant immunogenicity, telomerase is considered an ideal universal tumor-associated antigen, and consequently, a very attractive target for anti-cancer immunotherapy. To date, different telomerase targeting immunotherapies have been studied in pre-clinical and clinical settings, these approaches include peptide vaccination and cell-based vaccination. The objective of this review paper is to discuss the role of human telomerase in cancer immunotherapy analyzing recent developments and future perspectives in this field.
端粒酶是一种逆转录酶，可维持端粒长度，补偿每个复制周期中发生的染色体末端磨损。端粒酶在生殖细胞和干细胞中表达，而在成人体细胞中几乎检测不到。另一方面，端粒酶在大多数人类肿瘤中广泛表达，在癌细胞的复制行为和永生中起关键作用。多项研究表明，端粒酶衍生的肽能够结合I类和II类人类白细胞抗原（HLA）分子，并有效激活CD8和CD4 T细胞亚群。由于其在癌细胞中的广泛且选择性表达以及显著的免疫原性，端粒酶被认为是一种理想的通用肿瘤相关抗原，因此是抗癌免疫疗法非常有吸引力的靶点。迄今为止，已经在临床前和临床环境中研究了不同的靶向端粒酶的免疫疗法，这些方法包括肽疫苗接种和基于细胞的疫苗接种。这篇综述文章的目的是讨论人类端粒酶在癌症免疫疗法中的作用，分析该领域的最新进展和未来前景。
