In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. 4Department of Chemistry, Université de Montréal, Montréal, QC, Canada.

3Department of Medicine, Université de Montréal, Montréal, QC, Canada.2Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.1École Normale Supérieure de Lyon, Université Claude Bernard Lyon I, Université de Lyon, Lyon, France.Robin Minati 1,2, Claude Perreault 2,3* and Pierre Thibault 2,4* From Identified Tumor-Specific Antigens to Actionable Therapeutics: Validation and Selection.The Post-Transcriptional Antigens and Their Rising Interest for Immunotherapies.Endogenous Retroelements-Derived Tumor-Specific Antigens: A Predominant Source of Non-Mutated Antigens for a Vaccine Against Cancer.Gene Fusion Neoantigens Are Rather Rare but Recurrent Across Malignancies.Mutational-Frameshift Neoantigens: A Promising Source of Tumor-Specific Antigens for Renal Cell Carcinoma, Homologous Recombination-Deficient Tumors, and High Microsatellite Instability (MSI-H) Tumors.Single Nucleotide Variant Neoantigens: A Relatively Meager Source of Tumor-Specific Antigens for Immunotherapies.The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review.

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