CD4 and melanoma: However, in most cases, downregulation of MHC-I can be reversed by treatment with IFN-γ.39 In a number of clinical trials, for instance, in malignant melanoma,54,55 colon carcinoma56 and bladder cancer,57 IFN-γ treatment resulted in tumoral upregulation of MHC class I and de novo MHC class II expression and increased frequency of tumor-specific CD4+ T-cells.