PMID- 32585818 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 12 IP - 6 DP - 2020 Jun 23 TI - Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process. LID - 10.3390/cancers12061660 [doi] LID - 1660 AB - 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. FAU - Feola, Sara AU - Feola S AUID- ORCID: 0000-0002-4012-4310 AD - Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland. AD - Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland. AD - Translational Immunology Program (TRIMM), Faculty of Medicine, Haartmaninkatu 8, University of Helsinki, 00290 Helsinki, Finland. AD - Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, FI-00014 Helsinki, Finland. FAU - Chiaro, Jacopo AU - Chiaro J AUID- ORCID: 0000-0001-6577-2691 AD - Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland. AD - Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland. AD - Translational Immunology Program (TRIMM), Faculty of Medicine, Haartmaninkatu 8, University of Helsinki, 00290 Helsinki, Finland. AD - Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, FI-00014 Helsinki, Finland. FAU - Martins, Beatriz AU - Martins B AD - Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland. AD - Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland. AD - Translational Immunology Program (TRIMM), Faculty of Medicine, Haartmaninkatu 8, University of Helsinki, 00290 Helsinki, Finland. AD - Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, FI-00014 Helsinki, Finland. FAU - Cerullo, Vincenzo AU - Cerullo V AD - Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland. AD - Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland. AD - Translational Immunology Program (TRIMM), Faculty of Medicine, Haartmaninkatu 8, University of Helsinki, 00290 Helsinki, Finland. AD - Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki, FI-00014 Helsinki, Finland. LA - eng GR - 681219/Horizon 2020 Framework Programme/ GR - none/Helsinki Institute of Life Science (HiLIFE)/ GR - 19072019/Jane ja Aatos Erkon Saatio/ GR - none/Syopajarjestot/ PT - Journal Article PT - Review DEP - 20200623 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7352969 OTO - NOTNLM OT - cancer immunotherapy OT - epitope prediction OT - immunopeptidome OT - tumor antigens COIS- Vincenzo Cerullo is a cofounder and shareholder at VALO Therapeutics. The other authors have no conflicts of interest. EDAT- 2020/06/27 06:00 MHDA- 2020/06/27 06:01 PMCR- 2020/06/23 CRDT- 2020/06/27 06:00 PHST- 2020/04/29 00:00 [received] PHST- 2020/06/11 00:00 [revised] PHST- 2020/06/20 00:00 [accepted] PHST- 2020/06/27 06:00 [entrez] PHST- 2020/06/27 06:00 [pubmed] PHST- 2020/06/27 06:01 [medline] PHST- 2020/06/23 00:00 [pmc-release] AID - cancers12061660 [pii] AID - cancers-12-01660 [pii] AID - 10.3390/cancers12061660 [doi] PST - epublish SO - Cancers (Basel). 2020 Jun 23;12(6):1660. doi: 10.3390/cancers12061660.