Tumor-infiltrating CD3- NK cells are more effective than CD3+ T cells in killing autologous melanoma cells.
We have studied the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL) derived from eight human melanomas cultured for up to 60 d in the presence of recombinant IL-2. In the early period of the cultures, TIL were predominantly T cells of CD8+ phenotype and contained 10-30% of CD3- cells. Four of the five early TIL cultures tested in a cytotoxicity assay displayed a degree of MHC-unrestricted lysis on a series of autologous and allogenic melanoma cell lines as well as the K562 natural killer-sensitive target. With longer periods of time in culture, all TIL lines showed a decrease in lytic activity that was associated with the loss of CD3- cells. Thus, most of the killing of short-term TIL cultures appeared to be mediated by CD3- natural killer cells, whereas CD3+ T cells were found to be weak anti-tumor effectors. Even though the CD3+ T cells were not cytotoxic on K562 targets, their lytic activity (even weak) against melanoma cells appeared to be non-MHC restricted, and was blocked by anti-CD3 antibodies. In addition, cytotoxicity of the CD3+ TIL cultures was compared to that of a CD3-/NKH1+ cell line purified from peripheral blood. It was found that natural killer cells were much more potent than CD3+ TIL on the melanoma cell lines tested.
Azogui
O
O
Laboratoire d'Hémato-Immunologie, INSERM U333, Institut Gustave-Roussy, Villejuif, France.
Avril
M F
MF
Margulis
A
A
Guillard
M
M
Caillou
B
B
Prade
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001667:Binding, Competitive; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins