Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas

• Published in: PloS one Vol. 7; no. 11; p. e49878
• Main Authors: Cordova, Adriana, Toia, Francesca, La Mendola, Carmela, Orlando, Valentina, Meraviglia, Serena, Rinaldi, Gaetana, Todaro, Matilde, Cicero, Giuseppe, Zichichi, Leonardo, Donni, Paolo Li, Caccamo, Nadia, Stassi, Giorgio, Dieli, Francesco, Moschella, Francesco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.11.2012; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Biology; Biotechnology; Brain cancer; Breast cancer; Cancer therapies; Chemotherapy; Cytokines; Cytokines - biosynthesis; Cytotoxicity; Cytotoxicity, Immunologic; Developmental stages; Discipline; Effector cells; Female; Humans; Immune response; Immune system; Immunologic Memory; Immunophenotyping; Immunosurveillance; Immunotherapy; Interferon; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical prognosis; Medicine; Melanoma; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Metastases; Metastasis; Middle Aged; Neoplasm Staging; Patients; Phenotype; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T cell receptors; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor cell lines; Tumor cells; Tumor necrosis factor-α; Tumor-infiltrating lymphocytes; Tumors; Zoledronic acid; γ-Interferon; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0049878

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.