Relapse or Eradication of Cancer Is Predicted by Peptide-Major Histocompatibility Complex Affinity

被引:124
作者
Engels, Boris [1 ,2 ]
Engelhard, Victor H. [3 ,4 ]
Sidney, John [5 ]
Sette, Alessandro [5 ]
Binder, David C. [1 ,2 ]
Liu, Rebecca B. [1 ,2 ]
Kranz, David M. [6 ]
Meredith, Stephen C. [1 ,2 ]
Rowley, Donald A. [1 ,2 ]
Schreiber, Hans [1 ,2 ]
机构
[1] Univ Chicago, Dept Pathol, Comm Immunol, Chicago, IL 60637 USA
[2] Univ Chicago, Comm Canc Biol, Chicago, IL 60637 USA
[3] Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA
[4] Univ Virginia Hlth Syst, Carter Immunol Ctr, Charlottesville, VA 22908 USA
[5] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA
[6] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA
关键词
ANTIGEN-LOSS VARIANTS; MELANOMA ANTIGEN; T-LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY; QUANTITATIVE-ANALYSIS; ESTABLISHED TUMORS; SELF-TOLERANCE; IN-VITRO; CELL; RECOGNITION;
D O I
10.1016/j.ccr.2013.03.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro. We found that tumor eradication by T cells required high affinities of the targeted peptides for major histocompatibility complex (MHC) class I. Affinities of at least 10 nM were required for relapse-free regression. Only high-affinity peptide-MHC interactions led to efficient cross-presentation of antigen, thereby stimulating cognate T cells to secrete cytokines. These findings highlight the importance of targeting peptides with high affinity for MHC class I when designing T cell-based immunotherapy.
引用
收藏
页码:516 / 526
页数:11
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