Tumor progression despite efficient tumor antigen cross-presentation and effective "arming" of tumor antigen-specific CTL.
To determine whether APC function or "arming" of CTL for lytic function are the points at which Ags from a nonimmunogenic tumor fail to induce an effective immune response, we established a murine tumor model that expressed intracellular OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific CD8(+) T cells throughout tumor growth. Viable cOVA-9 tumor cells grew in normal mice at a rate similar to the parental tumor, and vaccination with irradiated cOVA-9 cells did not induce protection against itself or the parental line, confirming its nonimmunogenic status. In vivo evaluation during tumor growth demonstrated persisting tumor Ag cross-presentation accompanied by the generation of potent, specific CTL which were detectable when tumors were barely palpable. Despite the presence of highly active CTL in the tumor-draining lymph nodes, there was no apparent lysis of tumor-associated APC. These data show that tumor-draining APC are not dysfunctional with regard to two crucial processes, in vivo tumor Ag cross-presentation and specific CTL arming, and that failure to prevent tumor growth is not in the induction phase, but in the effector phase and occurs within the tumor itself before the tumor matrix is established.
Nelson
D J
DJ
Department of Medicine, University of Western Australia, Nedlands, Queen Elizabeth II Medical Center, Perth, Western Australia, Australia. delian@cyllene.uwa.edu.au
Mukherjee
S
S
Bundell
C
C
Fisher
S
S
van Hagen
D
D
Robinson
B
B
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018450:Disease Progression; D004527:Egg Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects / Q000637:transplantation
D000951:Antigens, Neoplasm; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin