Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine

Marialuisa Sensi, Cinthia Farina, Cristina Maccalli, Raffaella Lupetti, Gabriella Nicolini, Andrea Anichini, Giorgio Parmiani, David Berd

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Abstract

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 β-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.

Original languageEnglish
Pages (from-to)710-717
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number4
Publication statusPublished - 15 Feb 1997
Externally publishedYes

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Keywords

  • cytotoxic T cells
  • melanoma
  • T cell receptor
  • tumor-infiltrating lymphocytes
  • vaccine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sensi, M., Farina, C., Maccalli, C., Lupetti, R., Nicolini, G., Anichini, A., Parmiani, G., & Berd, D. (1997). Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine. Journal of Clinical Investigation, 99(4), 710-717.