Tumor-infiltrating lymphocytes exhibiting high ex vivo cytolytic activity fail to prevent murine melanoma tumor growth in vivo.
The identification of tumor-associated Ags recognized by CD8+ CTL and prevention of tumor outgrowth by adoptive transfer of these CTL demonstrates that CD8+ T cells play a major role in antitumor immunity. We have generated B16.F10 melanoma cells that express the glycoprotein epitope amino acid 33-41 (GP33) of the lymphocytic choriomeningitis virus (LCMV) to examine antitumor CD8+ T cell response in C57BL/6 mice immune to LCMV and in mice transgenic for the LCMV GP33-specific P14 TCR (P14 TCR mice). We find that B16.F10GP33 tumor cells grew in syngeneic C57BL/6 mice without inducing T cell tolerance. LCMV infection or adoptive transfer of LCMV-specific effector T cells delayed but did not prevent growth of preestablished tumors in these mice. However, B16.F10GP33 tumor cells were rejected in mice immune to LCMV and in mice treated with LCMV-specific effector T cells on the same day as the tumor. Surprisingly, B16.F10GP33 tumor cells grew in P14 TCR transgenic mice despite an abundance of tumor-associated Ag-specific CD8+ T cells. In these mice, freshly isolated tumor-infiltrating lymphocytes exhibited an activated phenotype and displayed high GP33-specific cytolytic activity when assessed ex vivo. Thus, B16.F10GP33 melanoma cells are able to initiate, but not to sustain, a GP33-specific CTL response sufficient to clear the tumor enduringly.
Prévost-Blondel
A
A
Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Germany.
Zimmermann
C
C
Stemmer
C
C
Kulmburg
P
P
Rosenthal
F M
FM
Pircher
H
H
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral; D002455:Cell Division / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus