Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas

PLoS One. 2012;7(11):e49878. doi: 10.1371/journal.pone.0049878. Epub 2012 Nov 26.

Abstract

T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1(+) and Vδ2(+) cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell, gamma-delta

Grant support

This work has been supported by grants from the Italian Ministry for Instruction, University and Research (contract no. 2008L57JXW to FD), the Italian Ministry of Health (Progetto ricerca finalizzata 2007 “Stem cells in different pathological conditions innovative therapeutical approches” to FD) and the University of Palermo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.