Reduced number and impaired function of circulating gamma delta T cells in patients with cutaneous primary melanoma.
We studied the peripheral representation, in vitro expansion, cytokine production, and cytotoxicity of gamma delta T lymphocytes from 23 patients with cutaneous primary melanoma and 28 healthy subjects. We demonstrated that the absolute number and the percentage of circulating gamma delta + T cells were significantly reduced in melanoma patients in comparison with healthy subjects. The decrease was due to a reduction of V delta 2 T cells, whereas the number of V delta 1 T cells was not affected. As a consequence, the V delta 2/V delta 1 ratio was inverted in melanoma patients. A lower percentage of gamma delta + T cells producing tumor necrosis factor-alpha or interferon-gamma was found in melanoma patients. After a 10 d in vitro culture, both the percentage and the expansion index of gamma delta T cells, and in particular of V delta 2 subset, were significantly reduced in melanoma patients in comparison with healthy subjects. The cytotoxicity of sorted gamma delta T cells against tumor cell lines and the percentage of gamma delta T cells producing perforins were preserved in melanoma patients. The numerical and functional impairment of gamma delta 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.
Argentati
Katy
K
Laboratory of Tumor Immunology, Immunology Center, I.N.R.C.A. Research Department, Ancona, Italy.
Re
Francesca
F
Serresi
Stefano
S
Tucci
Maria G
MG
Bartozzi
Beatrice
B
Bernardini
Giovanni
G
Provinciali
Mauro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma