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Critical Reviews™ in Immunology
IF: 1.404 5-Year IF: 3.347 SJR: 0.706 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i5.60
pages 485-493

Improving Immunotherapy by Conditionally Enhancing MHC Class I Presentation of Tumor Antigen-Derived Peptide Epitopes

Walter J. Storkus
Department of Dermatology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Christopher Herrem
Department of Dermatology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Mayumi Kawabe
Department of Dermatology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Peter A. Cohen
Center for Surgery Research, NE6-307, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Ronald M. Bukowski
Department of Immunology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA
James H. Finke
Department of Immunology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Amy K. Wesa
Department of Dermatology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA, and the Cleveland Clinic Foundation, Cleveland, OH 44195, USA

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.


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