Equilibrium between host and cancer caused by effector T cells killing tumor stroma

被引:63
作者
Zhang, Bin [1 ,2 ]
Zhang, Yi [2 ,3 ]
Bowerman, Natalie A. [4 ]
Schietinger, Andrea [2 ]
Fu, Yang Xin [2 ]
Kranz, David M. [4 ]
Rowley, Donald A. [2 ]
Schreiber, Hans [2 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, San Antonio Canc Inst, San Antonio, TX 78229 USA
[2] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[3] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA
[4] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA
关键词
D O I
10.1158/0008-5472.CAN-07-5324
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The growth of solid tumors depends on tumor stroma. A single adoptive transfer of CD8(+) CTLs that recognize tumor antigen-loaded stromal cells, but not the cancer cells because of MHC restriction, caused long-term inhibition of tumor growth. T cells persisted and continuously destroyed CD11b(+) myeloid-derived, F4/80(+) or Gr1(+) stromal cells during homeostasis between host and cancer. Using high-affinity T-cell receptor tetramers, we found that both subpopulations of stromal cells captured tumor antigen from surrounding cancer cells. Epitopes on the captured antigen made these cells targets for antigen-specific T cells. These myeloid stromal cells are immunosuppressive, proangiogenic, and phagocytic. Elimination of these myeloid cells allowed T cells to remain active, prevented neovascularization, and prevented tumor resorption so that tumor size remained stationary. These findings show the effectiveness of adoptive CTL therapy directed against tumor stroma and open a new avenue for cancer treatments.
引用
收藏
页码:1563 / 1571
页数:9
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