Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a hapten-modified autologous tumor vaccine.
Metastatic melanoma patients treated with an autologous DNP-modified tumor cell vaccine develop inflammatory responses in metastatic tumors characterized by infiltration of CD8+ T cells. To further define this immune response, we analyzed T cell receptor beta-chain variable (TCRBV) region repertoire in biopsy specimens and peripheral blood lymphocytes of six patients. After administration of DNP vaccine, a restricted set of TCRBV gene families was found to be expanded compared with prevaccine metastases. In several postvaccine lesions of one patient, obtained over a 2-yr period, TCRBV14+ T cells were clonally expanded and identical T cell clonotypes could be detected. Two major recurring clones were biased toward the use of TCRBJ1S5. Furthermore, T cell lines derived from two such infiltrated skin lesions and, enriched in TCRBV14+ T cells, displayed HLA-class I-restricted lysis of the autologous melanoma cells. Clonal expansion of T cells was demonstrated in the T cell-infiltrated, postvaccine metastasis of a second patient as well. These results indicate that vaccination with autologous, DNP-modified melanoma cells can expand selected clones of T cells at the tumor site and that such clones are potentially destructive to the tumor.
Sensi
M
M
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Farina
C
C
Maccalli
C
C
Lupetti
R
R
Nicolini
G
G
Anichini
A
A
Parmiani
G
G
Berd
D
D
D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006241:Haptens / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000556:secondary* / Q000628:therapy; D005810:Multigene Family / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D019496:Cancer Vaccines; D006680:HLA Antigens; D006241:Haptens; D016693:Receptors, Antigen, T-Cell, alpha-beta