Solid tumors "melt" from the inside after successful CD8 T cell attack.
Adoptive transfer of tumor-specific T cells represents a promising approach for cancer immunotherapy. Here, we visualized the anti-tumor response of CD8 T cells from P14 TCR-transgenic mice specific for the model antigen GP33 by immunohistology. P14 T cells, adoptively transferred into tumor-bearing hosts, induced regression of established 3LL-A9(GP33) and MCA102(GP33) tumors that express GP33 as a tumor-associated model antigen. Strikingly, the visible effects of P14 T cell attack, such as the destruction of the tumor vasculature and accumulation of granulocytes, were predominantly detected inside the tumor mass. In regressing tumors, P14 T cells were found in the intact rim zone but not in central areas that were infiltrated with granulocytes and lacked CD31(+) endothelial cells. The rim of P14 T cell-treated tumors showed an increase in vascular density and decrease in hypoxia compared to untreated tumors. Hypoxic areas of tumors are known to exhibit decreased sensitivity to radiation therapy or chemotherapy. Thus, our data also imply that adoptive transfer of tumor-specific CD8 T cells might synergize with radiation therapy or chemotherapy in the elimination of solid tumors in vivo.
Blohm
Ulrike
U
Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany.
Potthoff
Dan
D
van der Kogel
Albert J
AJ
Pircher
Hanspeter
H
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D000860:Hypoxia / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D011878:Radiotherapy
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019408:Platelet Endothelial Cell Adhesion Molecule-1