Expression of HLA-DR antigens on tumour cells does not contribute to skin reactivity to autologous cholesteryl hemisuccinate (CHS)-treated tumour cells in patients with metastatic melanoma

Abstract

Skin tests with autologous cholesteryl hemisuccinate (CHS)-treated and untreated cells were performed in ten metastatic melanoma patients. In the majority of cases evident reaction was noted with CHS-treated cells (9/10) while the reaction with untreated cells was mostly negative (7/10). Tumour cell suspensions used for skin tests were characterized for reactivity with monoclonal antibody TAL 1B5 detecting the HLA-DR alpha chain. There were no differences between CHS-treated and untreated cells with respect to HLA-DR expression and no correlation was found between grade of skin reaction to CHS-treated cells and the proportion of HLA-DR positive cells in the injected cell sample.

Increased Immunogenicity of Human Renal Carcinoma Cells following Treatment with Cholesterol Derivatives

“…It was sug gested that in the cholesteryl-hemisuccinate-rigidified membranes, the tumor-associated antigens are presum ably more exposed and in a closer physical association between themselves and with components of the major histocompatibility complexes. In fact, it has been dem onstrated more recently that HLA-DR antigens ex pressed on tumor cells did not contribute to the skin reactivity induced by homologous cholesteryl-hemisuccinate-treated tumor cells in patients with metastatic melanoma [27], Membrane fluidity is also influenced by the presence of hydroxysterols, and in particular by 25-hydroxycholesterol [17,18], This oxysterol becomes inserted in cel lular membranes, including plasma membrane [28], in which it induces specific morphologic and functional changes [18], However, as evidenced in the present data, 25-hydroxycholesterol decreased membrane fluidity in renal carcinoma cells, but failed to cause an increased immunogenicity in the same proportion of patients. At present, the physical techniques to measure membrane fluidity provide at best rough indications of membrane fluidity in comparative studies, but give little or no insight in lateral heterogeneity or domains of lipids that may exist in biological membranes [29], Thus, physico chemical properties of a putative lipidic microdomain surrounding the tumor antigens, rather than global mem brane lipid fluidity, may be critical for eliciting specific changes in their expression or conformational state on the cell surface.…”