The rate of the CD8-dependent initial reduction in tumor volume is not limited by contact-dependent perforin, Fas ligand, or TNF-mediated cytolysis.
Established EG7 tumors expressing OVA and growing at an intradermal site become rapidly reduced in size following adoptive therapy with in vitro-generated type I CD8 T cell (Tc1) effectors generated from naive CD8 T cells from transgenic TCR OVA-specific mice. Tc1 effectors kill EG7 target cells in vitro by a perforin-dependent mechanism. However, we show that there is no quantitative diminution of the initial phase of antitumor activity in vivo, whether the Tc1 effectors are derived from perforin-, Fas ligand-, or TNF-deficient transgenic TCR mice or whether the recipients are perforin deficient. Tumors are also equally well controlled whether the Tc1 effectors come from mice deficient in perforin plus Fas ligand or perforin plus TNF. Control of tumor growth is diminished when Tc1 effectors generated from IFN-gamma-deficient mice are used. We conclude that control of tumor growth is not in any way affected by loss of contact-mediated lytic mechanisms, and conclude that the CD8 effectors must act by recruiting host effector mechanisms to control tumor growth.
Hollenbaugh
Joseph A
JA
Trudeau Institute, Saranac Lake, NY 12983, USA.
Reome
Joyce
J
Dobrzanski
Mark
M
Dutton
Richard W
RW
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D004527:Egg Proteins / Q000276:immunology; D053222:Fas Ligand Protein; D016219:Immunotherapy, Adoptive; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology
D000951:Antigens, Neoplasm; D004527:Egg Proteins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; C110366:OVA-8; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D010047:Ovalbumin