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

J Clin Invest. 1997 Feb 15;99(4):710-7. doi: 10.1172/JCI119215.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cancer Vaccines / immunology*
  • Cell Line
  • Clone Cells
  • Gene Rearrangement, T-Lymphocyte / immunology
  • HLA Antigens / immunology
  • Haptens / pharmacology
  • Humans
  • Lung Neoplasms / immunology
  • Melanoma / immunology*
  • Melanoma / secondary*
  • Melanoma / therapy
  • Multigene Family / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Transcription, Genetic / immunology


  • Cancer Vaccines
  • HLA Antigens
  • Haptens
  • Receptors, Antigen, T-Cell, alpha-beta