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Effect of Recombinant Human Leukocyte, Fibroblast, and Immune Interferons on Expression of Class I and II Major Histocompatibility Complex and Invariant Chain in Early Passage Human Melanoma Cells¹

Experimental Oncology [P. N., R. T., P. G., I. D'A., P. G. N.] and Surgery Department [A. C.], Regina Elena Cancer Institute, Rome, Italy, and Departments of Neurosurgery, Pathology, and Urology, Cancer Center/Institute of Cancer Research, Columbia University College of Physicians and Surgeons, New York, New York 10032 [P. B. F.]

Twenty-five early-passage (8) melanoma cell lines, isolated from ten patients with metastatic melanoma, were analyzed by a combination of serological, immunochemical, and molecular methods for mRNA levels, synthesis, and surface expression of MHC class I and class II antigens prior to and following exposure to recombinant human leukocyte (IFN-A), fibroblast (IFN-ß), and immune (IFN-) interferon. All the cell lines expressed variable levels of HLA class I gene products that were up-regulated to different extents upon exposure to specific interferons (IFNs). HLA class II antigens were expressed in 22 of the 25 melanoma lines and IFN- increased the levels of class II mRNA, protein synthesis, and surface expression in all cultures displaying baseline expression. A significant up-regulation of class II antigen expression by IFN- or -ß, associated with higher levels of class II transcripts and enhanced synthesis, was found only in two early-passage human melanoma cell lines. In three lesions from the same patient which did not constitutively express class II antigens, no expression of these glycoproteins could be induced with any of the IFNs. These results indicate that IFN- does not act as a de novo inducer of class II antigen expression in early-passage human melanoma cell lines. This hypothesis is further supported by analysis of class II-associated invariant chain (Ii) expression, which is expressed and induced by IFNs in a manner similar to that of class II antigens. The present study also indicates that early-passage metastatic melanoma lesions from the same patient are heterogeneous in their de novo expression of major histocompatibility antigens and in their modulation by IFNs.

¹ This study was supported in part by Progetto Finalizzato CNR Biotechnologie e Biostrumentazione, by AIRC, and by National Cancer Institute Grant CA35675. P. B. F. is Chernow Research Scholar in the Departments of Neurosurgery, Pathology, and Urology, Columbia University, College of Physicians and Surgeons.

² To whom requests for reprints should be addressed, at Experimental Oncology, Regina Elena Cancer Institute, Viale Regina Elena, 291, 00161 Rome, Italy.

Received 9/25/89. Accepted 7/ 5/90.

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