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At the molecular level, this distinction is possible because tumoral cells undergo a series of genetic and epigenetic changes leading to the generation of new self-derived antigens which are generally termed tumor-specific antigens (TSAs) or neoantigens. Independently from their mechanisms of action, all of these therapies rely on the ability of the patientвЂ™s adaptive immune system to discriminate between healthy (i.e., normal or stressed) cells and cancerous ones. Several types of immunotherapies including vaccines ( 3), antibodies ( 4), oncolytic viruses ( 5), immune checkpoint inhibitor (ICI) therapies ( 6, 7), and T cell-based immunotherapies are currently used in the clinic. In contrast to classical treatment (i.e., surgery, chemotherapy, and radiation therapy) which target directly and aspecifically the tumoral cells, immunotherapies target the hostвЂ™s immune system to initiate, augment and/or reestablish an efficient antitumoral immune response ( 2). More recently, the Nobel prize award to Allison and Honjo, highlights the significance of immunotherapies, and how it changed the way we treat several types of cancers over the past decades. The selection of вЂњCancer immunotherapyвЂќ by the journal Science as the breakthrough of the year in 2013 ( 1) properly illustrates how promoting the patientsвЂ™ immune response against cancer cells has revolutionized the field of anticancer therapies. 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, UniversitГ© de MontrГ©al, MontrГ©al, QC, Canada.3Department of Medicine, UniversitГ© de MontrГ©al, MontrГ©al, QC, Canada.2Institute for Research in Immunology and Cancer, UniversitГ© de MontrГ©al, MontrГ©al, QC, Canada.1Г‰cole Normale SupГ©rieure de Lyon, UniversitГ© Claude Bernard Lyon I, UniversitГ© 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.

1755 old frontier mod