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[Cancer Research 61, 3718-3724, May 1, 2001]
© 2001 American Association for Cancer Research

Immunology

High Frequency of Cytolytic T Lymphocytes Directed against a Tumor-specific Mutated Antigen Detectable with HLA Tetramers in the Blood of a Lung Carcinoma Patient with Long Survival1

Vaios Karanikas, Didier Colau, Jean-François Baurain, Rita Chiari2, Joëlle Thonnard3, Ilse Gutierrez-Roelens, Céline Goffinet, Emile Van Schaftingen, Patrick Weynants, Thierry Boon and Pierre G. Coulie4

Cellular Genetics Unit [V.K., J-F.B, R.C., J.T., I.G-R., C.G., T.B., P.G.C.], and Biochemistry Unit [E.V.S.], Université de Louvain, B-1200 Brussels; Ludwig Institute for Cancer Research, Brussels Branch, B-1200 Brussels [D.C., P.W., T.B.]; and Service de Pneumologie et d’Anatomopathologie, Hôpital de Mont-Godinne, Université de Louvain, B-5530 Yvoir [P.W.], Belgium

We have identified an antigen recognized by autologous CTL on the lung carcinoma cells of a patient who enjoyed a favorable clinical evolution, being alive 10 years after partial resection of the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and encoded by a mutated sequence in the gene coding for malic enzyme, an essential enzyme that converts malate to pyruvate. In the tumor cell line derived from the patient, only the mutated malic enzyme allele is expressed, because of a loss of heterozygosity in the region of chromosome 6 that contains this locus. Tetramers of soluble HLA-A2 molecules loaded with the antigenic peptide stained ~0.4% of the patient’s blood CD8 T cells. When these cells were stimulated in clonal conditions, 25% of them proliferated, and the resulting clones were lytic and specific for the mutated malic enzyme peptide. T-cell receptor analysis indicated that almost all of these antimalic CTLs shared the same receptor. Antimalic T cells were consistently found in blood samples collected from the patient between 1990 and 1999, at frequencies ranging from 0.1 to 0.4% of the CD8 cells. Their frequency appeared to double within 2 weeks after intradermal inoculation of lethally irradiated autologous tumor cells. These results indicate that nonmelanoma cancer patients may also have a high frequency of blood CTLs directed against a tumor-specific antigen.




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Copyright © 2001 by the American Association for Cancer Research.