Cellular events accompanying regression of skin recurrences of breast carcinomas treated with intralesional injections of natural interferons alpha and gamma
Ozzello, L.; Habif, D.V.; De Rosa, C.M.; Cantell, K.
Cancer Research 52(17): 4571-4581
1992
ISSN/ISBN: 0008-5472 PMID: 1355007 Document Number: 396245
Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections of nIFNs .alpha. and .gamma. delivered in combination (7 lesions) or singly (11 with nIFN-.alpha., one with nIFN-.gamma.). Histologically confirmed complete regressions occurred in 5 of 7 lesions treated with nIFN-.alpha./nIFN-.gamma. are in 5 of 11 recurrences injected with nIFN-.alpha. alone. In all cases specimens were obtained before and after therapy. In addition, in some cases (4 treated with nIFN-.alpha./nIFN-.gamma., 2 with nIFN-.alpha., one with nIFN-.gamma.) 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-.alpha./nIFN-.gamma. 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.