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The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA‐DR antigens on the tumor cells
Author(s) -
Taramelli Donatella,
Fossati Giuseppe,
Balsari Andrea,
Marolda Raffaele,
Parmiani Giorgio
Publication year - 1984
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910340610
Subject(s) - cytotoxic t cell , antigen , immunology , melanoma , interleukin 2 , monoclonal antibody , biology , tumor antigen , in vitro , immunotherapy , cancer research , antibody , immune system , biochemistry
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‐γ) 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.