The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA-DR antigens on the tumor cells
Articolo
Data di Pubblicazione:
1984
Citazione:
The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA-DR antigens on the tumor cells / D. Taramelli, G. Fossati, A. Balsari, R. Marolda, G. Parmiani. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 34:6(1984 Dec 15), pp. 797-806. [10.1002/ijc.2910340610]
Abstract:
Previous studies indicated that peripheral blood lymphocytes from patients (Pt-PBL) with lymph node metastatic melanomas proliferated in vitro and developed into tumor-restricted cytotoxic lymphocytes in response to alloantigens or interleukin 2 (IL-2). However, Pt-PBL were not stimulated by irradiated autologous metastatic melanoma (Auto-Me) cells. In the present study we report that the lack of stimulatory activity of Auto-Me cells may be due to a suppressive effect exerted by Auto-Me cells on the responder lymphocytes. In fact, we found that in 62% of cases examined, the addition of 5-10% Auto-Me cells to Pt-PBL cultures strongly inhibited both proliferation and the generation of tumor cytotoxic lymphocytes induced by alloantigens or IL-2. The inhibition was dose-dependent and tumor-restricted, and was not due either to toxicity, medium depletion or IL-2 absorption by Auto-Me cells. Normal fibroblasts, K562 cells and autologous E-lymphocytes were not suppressive. Auto-Me cells were able to inhibit Pt-PBL responses only when added during the first 24 h of culture and not later. Phenotypic analysis of Auto-Me cells using monoclonal antibodies directed against HLA-A,B,C, HLA-DR and melanoma-associated antigens revealed that the expression of high levels of DR antigens on Auto-Me cells was associated with an elevated suppressive activity. Conversely, Auto-Me cells with low or undetectable levels of DR antigens were not inhibitory. Furthermore, the increased expression of DR antigens on Auto-Me cells obtained by in vitro treatment with human interferon gamma (IFN-gamma) also resulted in an increased suppressive activity. We conclude that HLA-DR+ metastatic melanoma cells can interfere with the generation of an anti-tumor immune response, thus potentially favoring the escape of the tumor from the host's control mechanism.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
HLA-DR antigens; histocompatibility antigens class II; humans; interleukin-2; kinetics; lymphatic metastasis; melanoma; lymphocyte activation
Elenco autori:
D. Taramelli, G. Fossati, A. Balsari, R. Marolda, G. Parmiani
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