title: Improving immunotherapy by conditionally enhancing MHC class I presentation of tumor antigen-derived Peptide epitopes.
abstract: Tumors represent an altered self cell type that can be recognized by both the host humoral (B cells, antibodies) and cellular (T cells) adaptive immune systems. Because most known tumor-associated antigens (TAA) recognized by T cells represent overexpressed or aberrantly expressed proteins, which are not mutated and to which tolerance has been developed, the anti-TAA T-cell repertoire available to the cancer patient is of moderate-to-low avidity. Specific vaccinations typically amplify the absolute number of such T cells, but may have little consequence on improving their functional avidity, which may fall below a critical threshold required for effective recognition of tumor cells in situ. This review will discuss methods to improve low-avidity T-cell recognition of cancer cells by manipulating the tumor cells themselves to conditionally express higher levels of TAA-derived peptide epitopes presented in major histocompatibility (MHC) complexes. This may facilitate the design and performance of novel combinational therapies for the effective treatment of a broad range of cancer types.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, PA 15213, USA. storkuswj@upmc.edu
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: Christopher
authors.initials: C
authors.lastname: Herrem
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawabe
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cohen
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: James H
authors.initials: JH
authors.lastname: Finke
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wesa
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008285:Major Histocompatibility Complex / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010455:Peptides