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Open AccessReview

Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

by Sara Feola 1,2,3,4, Jacopo Chiaro 1,2,3,4, Beatriz Martins 1,2,3,4 and Vincenzo Cerullo 1,2,3,4,*
Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland
Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland
Translational Immunology Program (TRIMM), Faculty of Medicine, Haartmaninkatu 8, University of Helsinki, 00290 Helsinki, Finland
Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, FI-00014 Helsinki, Finland
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1660;
Received: 29 April 2020 / Revised: 11 June 2020 / Accepted: 20 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Antigens and Cancer Therapy)
According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field. View Full-Text
Keywords: tumor antigens; immunopeptidome; cancer immunotherapy; epitope prediction tumor antigens; immunopeptidome; cancer immunotherapy; epitope prediction
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Feola, S.; Chiaro, J.; Martins, B.; Cerullo, V. Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process. Cancers 2020, 12, 1660.

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