Cellular Events Accompanying Regression of Skin Recurrences of Breast Carcinomas Treated with Intralesional Injections of Natural Interferons α and γ¹

Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections of nIFNs α and γ delivered in combination (7 lesions) or singly (11 with nIFN-α, one with nIFN-γ). Histologically confirmed complete regressions occurred in 5 of 7 lesions treated with nIFN-α/nIFN-γ and in 5 of 11 recurrences injected with nIFN-α alone. In all cases specimens were obtained before and after therapy. In addition, in some cases (4 treated with nIFN-α/nIFN-γ, 2 with nIFN-α, one with nIFN-γ) multiple recurrences were injected simultaneously and were excised 24 h after 1, 3, and 10 injections and 21 days after completion of therapy. The main findings observed in the treated lesions undergoing complete and partial regressions included: (a) inhibition of mitotic activity and up-regulation of antigenic expression (mammary epithelial membrane antigen, intercellular adhesion molecule 1, HLA-DR) by the carcinoma cells; (b) activation of macrophages and dendrocytes with marked expression of HLA-DR and HLA-A,B,C; (c) infiltration of the dermis and tumors by activated T-lymphocytes (CD3⁺, CD4⁺, CD8⁺); (d) questionable participation by B-lymphocytes and natural killer cells; (e) activation of endothelium with enhancement of antigenic expression (intercellular adhesion molecule 1, HLA-DR), procoagulant activity, and vascular permeability. The responses elicited by nIFN-α/nIFN-γ were greater than those caused by either IFN used alone. It appears that in these patients the IFNs exerted an antiproliferative action and potentiated a cell-mediated immunological response liminally present in the neoplastic tissues prior to therapy.