Equilibrium between host and cancer caused by effector T cells killing tumor stroma.
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.
Zhang
Bin
B
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois, USA. Zhangb3@uthscsa.edu
Zhang
Yi
Y
Bowerman
Natalie A
NA
Schietinger
Andrea
A
Fu
Yang-Xin
YX
Kranz
David M
DM
Rowley
Donald A
DA
Schreiber
Hans
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D000939:Epitopes; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D010587:Phagocytosis; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000951:Antigens, Neoplasm; D000939:Epitopes