BACKGROUND: Melanoma is an immunogenic tumour but, despite the wide range of immunotherapies tested, only few promising results have been reported to date. Both in vitro and in xenograft models, γδ lymphocyte-mediated cytotoxicity against melanoma cells has been reported. IL-2/zoledronate treatment can expand γδ cells in vitro and in animal models. This could represent an immunotherapeutic strategy against melanoma. To evaluate the feasibility of this approach, we studied γδ lymphocyte phenotype from patients with melanoma, their ability to be expanded by IL-2/zoledronate and their cytotoxic activity against SK-MEL-30 cell line. MATERIALS AND METHODS: Peripheral blood samples were collected from 30 patients with melanoma and 10 healthy donors. Percentage of γδ lymphocytes and CD45RO+CD27+, CD45RA+CD27-, CD57+, Vγ9Vδ2 subpopulations were evaluated by flow cytometry. IL-2/zoledronate γδ cell expansion rate and their cytotoxicity against SK-MEL-30 cell line were studied. RESULTS: A percentage decrease in circulating Vγ9Vδ2 and an increase in CD45RA+CD27- and CD57+ γδ lymphocytes were observed in melanoma. IL-2/zoledronate expansion rate did not differ between controls and patients with melanoma but cytotoxicity against SK-MEL-30 appeared reduced. CONCLUSIONS: Our results show that γδ cell function is impaired in patients with advanced melanoma and suggest a possible role in tumour progression.
BACKGROUND:Melanoma is an immunogenic tumour but, despite the wide range of immunotherapies tested, only few promising results have been reported to date. Both in vitro and in xenograft models, γδ lymphocyte-mediated cytotoxicity against melanoma cells has been reported. IL-2/zoledronate treatment can expand γδ cells in vitro and in animal models. This could represent an immunotherapeutic strategy against melanoma. To evaluate the feasibility of this approach, we studied γδ lymphocyte phenotype from patients with melanoma, their ability to be expanded by IL-2/zoledronate and their cytotoxic activity against SK-MEL-30 cell line. MATERIALS AND METHODS: Peripheral blood samples were collected from 30 patients with melanoma and 10 healthy donors. Percentage of γδ lymphocytes and CD45RO+CD27+, CD45RA+CD27-, CD57+, Vγ9Vδ2 subpopulations were evaluated by flow cytometry. IL-2/zoledronate γδ cell expansion rate and their cytotoxicity against SK-MEL-30 cell line were studied. RESULTS: A percentage decrease in circulating Vγ9Vδ2 and an increase in CD45RA+CD27- and CD57+ γδ lymphocytes were observed in melanoma. IL-2/zoledronate expansion rate did not differ between controls and patients with melanoma but cytotoxicity against SK-MEL-30 appeared reduced. CONCLUSIONS: Our results show that γδ cell function is impaired in patients with advanced melanoma and suggest a possible role in tumour progression.
Authors: Kilian Wistuba-Hamprecht; Alexander Martens; Karin Haehnel; Marnix Geukes Foppen; Jianda Yuan; Michael A Postow; Phillip Wong; Emanuela Romano; Amir Khammari; Brigitte Dreno; Mariaelena Capone; Paolo A Ascierto; Ilja Demuth; Elisabeth Steinhagen-Thiessen; Anis Larbi; Bastian Schilling; Dirk Schadendorf; Jedd D Wolchok; Christian U Blank; Graham Pawelec; Claus Garbe; Benjamin Weide Journal: Eur J Cancer Date: 2016-07-09 Impact factor: 9.162
Authors: Mohd Wajid A Khan; Stuart M Curbishley; Hung-Chang Chen; Andrew D Thomas; Hanspeter Pircher; Domenico Mavilio; Neil M Steven; Matthias Eberl; Bernhard Moser Journal: Front Immunol Date: 2014-07-23 Impact factor: 7.561