TY - JOUR
T1 - Equilibrium between host and cancer caused by effector T cells killing tumor stroma
AU - Zhang, Bin
AU - Zhang, Yi
AU - Bowerman, Natalie A.
AU - Schietinger, Andrea
AU - Fu, Yang Xin
AU - Kranz, David M.
AU - Rowley, Donald A.
AU - Schreiber, Hans
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=40449105940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40449105940&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-5324
DO - 10.1158/0008-5472.CAN-07-5324
M3 - Article
C2 - 18316622
AN - SCOPUS:40449105940
SN - 0008-5472
VL - 68
SP - 1563
EP - 1571
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -