Activation markers on T cells infiltrating melanoma metastases after therapy with dinitrophenyl-conjugated vaccine (original) (raw)

Abstract

Treatment of metastatic melanoma patients with an autologous vaccine modified by the hapten, dinitrophenyl (DNP), produces a striking immunological effect: the induction of clinically evident inflammatory responses in metastatic tumors. Histological examination shows these tumors to be infiltrated with T lymphocytes. We studied the expression of activation markers on those cells and compared them with matched peripheral blood lymphocytes (PBL) and with lymphocytes extracted from metastases before treatment with DNP-conjugated vaccine. The median fraction of cells that were T cells in post-vaccine tumors was 41%, as compared with 9% in pre-treatment tumors, and those T cells were predominantly CD8+ (mean CD8/CD4 ratio=5.0). A high proportion of both pre- and posttreatment infiltrating T cells expressed HLA-DR (mean±SE=48%±4%), CD69 (56%±7%), and ganglioside GD3 (68%±5%). This distinguished them from matched PBL in which expression of those markers was significantly lower (HLA-DR=10%±2%; CD69=2%±0.4%; GD3=49%±4%). These changes were not accompanied by increased cell-surface expression of interleukin-2 (IL-2) receptors, either CD25 or p75, which were expressed by 1%–2% and 12% of tumor-infiltrating lymphocytes (TIL), respectively. The pattern of activation marker expression that we identified appears to be characteristic of tissue T cells with the memory phenotype. The low expression of IL-2 receptors could indicate functional impairment of TIL in situ, perhaps because of inhibitory molecules produced by melanoma cells.

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Authors and Affiliations

  1. Division of Neoplastic Diseases, Thomas Jefferson University, 1015 Walnut St., Suite 1005, 19107, Philadelphia, PA, USA
    David Berd, Henry C. Maguire Jr. & Michael J. Mastrangelo
  2. Department of Dermatology, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA, USA
    George Murphy

Authors

  1. David Berd
  2. Henry C. Maguire Jr.
  3. Michael J. Mastrangelo
  4. George Murphy

Additional information

This work was supported by NIH grants CA 39248, CA 40358, and AR 39674 from the National Institutes of Health and by funds from the Nat Pincus Trust

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Berd, D., Maguire, H.C., Mastrangelo, M.J. et al. Activation markers on T cells infiltrating melanoma metastases after therapy with dinitrophenyl-conjugated vaccine.Cancer Immunol Immunother 39, 141–147 (1994). https://doi.org/10.1007/BF01533378

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