Spontaneous regression of Sinclair swine cutaneous malignant melanoma

The Sinclair swine model of cutaneous malignant melanoma (SSCM) has been established and accepted by the scientific community. One of the unique phenomena observed in SSCM is the spontaneous regression that occurs in all animals except the 5 to 10% that die of complications associated with metastatic disease. We described the chronology of the regression and the cellular components at each phase. Histopathological analysis of tumor biopsies obtained throughout the first 6 mo of life revealed 1) tumors were present at birth and proliferated over the first 3 wk of life, 2) an infiltration of macrophages (M phi s) between the third and sixth wk was associated with a loss of melanoma cells, 3) between the second and third mo of age, a reproliferation of melanoma cells that escaped regression was observed and 4) by approximately 4 mo of age, an infiltration of lymphocytes occurred which was associated with the eventual loss of all melanoma cells and their replacement by scar tissue. Several lines of research have been initiated to determine the mechanism(s) responsible for the regression. Apoptotic melanoma cells have been observed in both tumor tissue and SSCM cell lines. We determined the sensitivity to apoptosis inducers varies among the established cell lines. Extensive telomeric associations between and within chromosomes in the form of dicentric, tricentric and ring configurations, which usually lead to cell death, have been observed. TNF alpha exhibited antiproliferative activity in several established SSCM cell lines. Melanoma cells were shown to release a factor(s) that inhibits TNF alpha expression in tumor associated M phi s. TGF has been shown to be antiproliferative at a dose of 0.1 ng in all cell lines tested. Mononuclear leukocytes were isolated from excised cutaneous melanomas (TIL) and peripheral blood (PBL). Flow cytometric analysis revealed higher percentages of CD8+ T-lymphocytes in tumor suspensions than in PBL. CD4+ T-lymphocytes were detected in larger numbers in peripheral blood. Virtually all TIL were MHC class II+; whereas, the percentages of PBL expressing this antigen were lower These studies provide data to support further research on the role of the cellular immune system and apoptosis in regression of SSCM.