Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.
Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation.
Mocellin
Simone
S
Department of Oncological & Surgical Sciences, University of Padova, via Giustianiani 2, 35128 Padova, Italy. simone.mocellin@unipd.it
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Donato
D
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019139:Tumor Escape
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D018836:Inflammation Mediators; D011948:Receptors, Antigen, T-Cell