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The effect of interferons on cellular differentiation

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Conclusion

The influence of IFN on cellular differentiation is well established in a variety of in vitro models such as Friend erythroleukemia, HL-60 cells or monocyte-macrophage differentiation. The exact effect of interferon, however, differs in special experimental situations. Enhancement of inhibition of terminal differentiation is possible, special subtypes of IFN may act only in a certain model and the effect is sometimes markedly dose dependent. The biochemical basis for the differentiation inducing activity of IFN is unknown, but studies reviewed here suggest that mechanisms different from those inducing the antiviral state are operative. Modulation of oncogene expression may be involved in some differentiation models. Various chemical substances (e. g. TPA, DMSO, retinoic acid) act synergistically with IFN in vitro. Furthermore, it appears that in vivo cellular differentiation processes are regulated by a combined action of IFN and other endogenously produced protein substances. IFN has already been shown to be effective in a small number of malignancies such as hairy cell leukemia, CML, renal carcinoma or non-Hodgkin lymphoma while it shows no or very limited effect in most solid tumors. The exact mechanism of IFN action and the proper dosage for clinical use, however, are still far from being settled. If these problems can be solved, IFN treatment, possibly as part of a multiple agent therapy, may turn out to be useful in future cancer therapy.

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  1. Institute of Virus Research, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900, Heidelberg, Federal Republic of Germany

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Moritz, T., Kirchner, H. The effect of interferons on cellular differentiation. Blut 53, 361–370 (1986). https://doi.org/10.1007/BF00321098

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