Marked heterogeneity for susceptibility to lysis by autologous CTL clones and allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with the highest susceptibility to lysis had increased ICAM-1 antigen expression. Phenotype analysis for the presence of extracellular matrix receptors in the β1- and β3-integrin families revealed that the tumor clones with the highest susceptibility to lysis were also characterized by frequent expression or increased expression of multiple receptors in the β1 family including VLA-1, -2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility to lysis, seen at the clonal level, was confirmed by selection experiments on the uncloned metastasis Me655/2. In fact, the neoplastic population surviving 3 cycles of immunoselection with IL-2-activated lymphocytes exhibited, in comparison to the unselected metastasis: (1) reduced susceptibility to lysis and (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens were observed on melanoma cells recovered after invading a reconstituted basement membrane. These data indicate that melanoma cells with enhanced susceptibility to cell-mediated lysis can be identified on the basis of phenotypic characteristics (ICAM-1 and VLA antigen profile) and functional features (invasive ability on reconstituted basement membranes).
ASJC Scopus subject areas
- Cancer Research