Abstract
Telomerase reverse transcriptase (TERT) plays a central role in the biology normal somatic cells and is a factor of primary relevance in cancer cells. Telomerase regulates telomere length and integrity during replicative cycles by adding TTAGGG sequences to the end of chromosomes. In normal cells, this process only permits a finite number of replicative events at the end of which telomere attrition triggers cellular growth arrest, senescence, and apoptosis. In transformed cancer cells, telomerase is constitutively activated, preventing telomere attrition and enabling continuous cell replication. TERT is quasi-ubiquitous in cancer cells and, consequently, is an ideal self-tumor antigen. In this review, we discuss the biology of TERT, its regulation in relation to cancer cell biology, and its putative role in immune surveillance. We place emphasis on adaptive immunity mediated by CD4 and CD8 T cells as these cells are the main contributors to immune surveillance, an immune defense against cancer cells that can be strenghtened by vaccination. We also discuss the existing data on TERT T cell responses in conjunction with immune checkpoint blockade therapy. Furthermore, since the activation of adaptive T cell immunity requires presentation of antigen by molecules of the major histocompatibility complex (MHC), we discuss the immunogenicity of TERT in relation to the MHC. We review past data generated using peptides identified through laborious approaches and provide a population level analysis of TERT-MHC interactions. The considerations made in this article may be helpful to direct future work aiming at developing TERT-based immunotherapies to fight ongoing cancer or prevent its development.
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Funding This work was supported in part by grant NIH RO1 CA220009 to M.Z. and H.C. and a Mark Foundation Emerging Leader Award 18-022-ELA to H.C.
Disclosure of Interests
MZ is on the Board of Invectys Inc., a biotechnology company with interest in a telomerase vaccine. All other authors declare no conflict of interest.
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Dosset, M., Castro, A., Xian, S., Carter, H., Zanetti, M. (2022). Telomerase Reverse Transcriptase in Humans: From Biology to Cancer Immunity. In: Rezaei, N. (eds) Cancer Research: An Interdisciplinary Approach. Interdisciplinary Cancer Research, vol 1. Springer, Cham. https://doi.org/10.1007/16833_2022_49
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