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Impaired function of gamma-delta lymphocytes in melanoma patients

Iacopo Petrini1, Simone Pacini, Sara Galimberti

  • 1Department of Oncology, Transplant and New Advances in Medicine, BIOS, Pisa University, Pisa, Italy. m.petrini@med.unipi.it

European Journal of Clinical Investigation
|July 11, 2012
PubMed
Abstract

Insights

Gamma delta (γδ) T-cells show impaired function in advanced melanoma patients, with reduced cytotoxicity against cancer cells. This suggests a potential role for these immune cells in melanoma progression.

Area of Science:

  • Immunology
  • Oncology
  • Cellular Biology

Background:

  • Melanoma is an immunogenic tumor with limited immunotherapy success.
  • Gamma delta (γδ) T-lymphocyte-mediated cytotoxicity against melanoma has been demonstrated in preclinical models.
  • Interleukin-2 (IL-2)/zoledronate can expand γδ T-cells, suggesting a potential immunotherapy strategy.

Purpose of the Study:

  • To investigate the phenotype of γδ T-lymphocytes in melanoma patients.
  • To assess the expansion capacity of γδ T-cells using IL-2/zoledronate.
  • To evaluate the cytotoxic activity of γδ T-cells against the SK-MEL-30 melanoma cell line.

Main Methods:

  • Flow cytometry was used to analyze γδ T-lymphocyte subsets in peripheral blood from 30 melanoma patients and 10 healthy donors.
  • The expansion rate of γδ T-cells treated with IL-2/zoledronate was measured.
  • Cytotoxicity assays were performed against the SK-MEL-30 cell line.

Main Results:

  • Melanoma patients exhibited a decreased percentage of circulating Vγ9Vδ2 γδ T-cells and an increased proportion of CD45RA+CD27- and CD57+ γδ T-cells.
  • IL-2/zoledronate expansion rates were comparable between melanoma patients and healthy controls.
  • Cytotoxicity of γδ T-cells against SK-MEL-30 cells was reduced in melanoma patients.

Conclusions:

  • Gamma delta (γδ) T-cell function appears to be impaired in patients with advanced melanoma.
  • These findings suggest a potential role for dysfunctional γδ T-cells in melanoma tumor progression.

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