INVOLVEMENT OF MHC CLASS-I MOLECULE AND ICAM-1 IN THE ENHANCEMENT OF ADHESION AND CYTOTOXIC SUSCEPTIBILITY TO IMMUNE EFFECTOR-CELLS OF TUMOR-CELLS TRANSFECTED WITH THE INTERLEUKIN (IL)-2, IL-4 OR IL-6 GENE

To investigate the molecular and cellular mechanisms involved in the r educed tumorigenicity and increased immunogenicity of interleukin-2 (I L-2)-, IL-4-or IL-6-gene-transfected B16 melanoma vaccine, we have ana lyzed the functional and phenotypic properties of these genetically en gineered melanoma cells in the present study. The cytokine-gene-transf ected B16 melanoma cells showed stronger adhesion to the lymphokine-ac tivated killer (LAK) cells or cytotoxic T lymphocytes (CTL), and highe r sensitivity to cytotoxicity of LAK cells or CTL. Using fluorescence- activated cell sorting analysis, we found that both MHC class I and IC AM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfect ion. The increased level of MHC class I and ICAM-1 expression seems to be responsible for the high sensitivity of these gene-transfected B16 cells to LAK or CTL cytotoxicity because anti-(MHC class I) or anti-I CAM-1 mAb could inhibit the adhesion and cytotoxicity increment simult aneously. The CTL induction was partly inhibited by anti-ICAM-1 mAb an d was completely blocked by anti-MHC class I mAb. These results sugges ted that the decreased tumorigenicity of IL-2-, IL-4-, and IL-6-gene-t ransfected B16 melanoma cells may be partly due to the increased sensi tivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cyt okine gene transfection.