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

Bin Zhang, Yi Zhang, Natalie A. Bowerman, Andrea Schietinger, Yang Xin Fu, David M. Kranz, Donald A. Rowley, Hans Schreiber

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1563-1571
Number of pages9
JournalCancer Research
Volume68
Issue number5
DOIs
StatePublished - Mar 1 2008

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T-Lymphocytes
Neoplasms
Stromal Cells
Neoplasm Antigens
Myeloid Cells
Antigens
Adoptive Transfer
Immunosuppressive Agents
Growth
T-Cell Antigen Receptor
Epitopes
Homeostasis
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, B., Zhang, Y., Bowerman, N. A., Schietinger, A., Fu, Y. X., Kranz, D. M., ... Schreiber, H. (2008). Equilibrium between host and cancer caused by effector T cells killing tumor stroma. Cancer Research, 68(5), 1563-1571. https://doi.org/10.1158/0008-5472.CAN-07-5324

Equilibrium between host and cancer caused by effector T cells killing tumor stroma. / Zhang, Bin; Zhang, Yi; Bowerman, Natalie A.; Schietinger, Andrea; Fu, Yang Xin; Kranz, David M.; Rowley, Donald A.; Schreiber, Hans.

In: Cancer Research, Vol. 68, No. 5, 01.03.2008, p. 1563-1571.

Research output: Contribution to journalArticle

Zhang, B, Zhang, Y, Bowerman, NA, Schietinger, A, Fu, YX, Kranz, DM, Rowley, DA & Schreiber, H 2008, 'Equilibrium between host and cancer caused by effector T cells killing tumor stroma', Cancer Research, vol. 68, no. 5, pp. 1563-1571. https://doi.org/10.1158/0008-5472.CAN-07-5324
Zhang, Bin ; Zhang, Yi ; Bowerman, Natalie A. ; Schietinger, Andrea ; Fu, Yang Xin ; Kranz, David M. ; Rowley, Donald A. ; Schreiber, Hans. / Equilibrium between host and cancer caused by effector T cells killing tumor stroma. In: Cancer Research. 2008 ; Vol. 68, No. 5. pp. 1563-1571.
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