Reduced Number and Impaired Function of Circulating γδ T Cells in Patients with Cutaneous Primary Melanoma

We studied the peripheral representation, in vitro expansion, cytokine production, and cytotoxicity of γδ T lymphocytes from 23 patients with cutaneous primary melanoma and 28 healthy subjects. We demonstrated that the absolute number and the percentage of circulating γδ+ T cells were significantly reduced in melanoma patients in comparison with healthy subjects. The decrease was due to a reduction of Vδ2 T cells, whereas the number of Vδ1 T cells was not affected. As a consequence, the Vδ2/Vδ1 ratio was inverted in melanoma patients. A lower percentage of γδ+ T cells producing tumor necrosis factor-α or interferon-γ was found in melanoma patients. After a 10 d in vitro culture, both the percentage and the expansion index of γδ T cells, and in particular of Vδ2 subset, were significantly reduced in melanoma patients in comparison with healthy subjects. The cytotoxicity of sorted γδ T cells against tumor cell lines and the percentage of γδ T cells producing perforins were preserved in melanoma patients. The numerical and functional impairment of γδ T cells could contribute to the inadequate immune response found in melanoma patients and offers the potentiality for the planning of new approaches of immune therapy of malignant melanoma