Intralesional selection of T cell clonotypes in the immune response to melanoma antigens occurring during vaccination.
T cells infiltrating pre- and postvaccine metastases obtained from melanoma patients vaccinated with either dinitrophenyl (DNP)-modified autologous tumor or with the MAGE-3.A1 peptide display selective T cell receptor (TCR) beta chain variable region (BV) repertoire changes at the tumor site as a consequence of vaccination. Restricted sets of BV families expand in all postvaccine lesions when compared with prevaccine specimens and often contain dominant clones. A protocol devised to obtain T cell lines highly enriched for expression of a given BV region through the use of anti-BV monoclonal antibodies was used to understand whether responses to specific antigen(s) accounted for these clonal expansions. In one of the patients vaccinated with DNP-modified tumor cells, BV-driven selection of the T lymphocytes expanded in two infiltrated postvaccine metastases resulted in T cell lines able to exert HLA class I-restricted lysis of the autologous tumor. These results indicate that TCR repertoire analysis at the tumor site facilitates the detection of T cell responses elicited by a vaccine and potentially cytotoxic for the autologous tumor.
Sensi
M
M
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Farina
C
C
Maccalli
C
C
Anichini
A
A
Berd
D
D
Parmiani
G
G
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines; D002999:Clone Cells / Q000276:immunology; D003001:Cloning, Molecular; D004140:Dinitrophenols / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004140:Dinitrophenols; D016693:Receptors, Antigen, T-Cell, alpha-beta