Human tumour-induced inhibition of interferon action in vitro: Reversal of inhibition by ?-carotene (pro-vitamin A)

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Abstract
Inhibitors of human interferon action that might be relevant to tumour resistance or escape mechanisms were investigated in a macrophage system. The effects of IFN on macrophage Fcγ receptor expression were inhibited by three preparations: (1) a low-molecular-weight component of normal autologous serum; (2) a low-molecular-weight component of carcinoma supernatant; and (3) physiological concentrations of retinol and retinoic acid. Since human carcinoma tissue contains abnormally high levels of retinoic acid-binding protein, the possibility that a tumour-associated retinoid contributes to tumour-induced inhibition in vitro was investigated. Inhibition of IFN action in vitro by retinoic acid (vitamin A acid) was found to be reversed by β-carotene (pro-vitamin A). When tested in the tumour system β-carotene also reversed inhibition by the human-carcinoma-derived signal. These data are consistent with the view that at least one of the tumour-derived signals inhibitory towards IFN is a tumour-associated retinoid, although firm evidence for this must await further physicochemical characterization of the inhibitory signal(s). The present data clearly show, nevertheless, that human tumour-induced inhibition of IFN in vitro can be reversed by the pro-vitamin β-carotene.