The Role of MHC Class I Glycoproteins in the Regulation of Induction of Cell Death in Immunocytes by Malignant Melanoma Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (4), p.1740-1744
• Main Authors: Fishman, Daniel, Irena, Brodyanski, Kellman-Pressman, Sigal, Karas, Michael, Segal, Shraga
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Apoptosis; Apoptosis - immunology; Biological Sciences; Cells; Cellular immunity; Coculture techniques; Fas Ligand Protein; Glycoproteins; Glycoproteins - immunology; H-2 Antigens - genetics; H-2 Antigens - immunology; Histocompatibility Antigens Class I - immunology; Immunology; Lymphocytes; Lymphocytes - immunology; Melanoma; Melanoma - immunology; Melanoma, Experimental - immunology; Membrane Glycoproteins - biosynthesis; Mice; Mice, Inbred C57BL; Proteins; Skin; Spleen - cytology; Spleen - immunology; Spleen cells; Splenocytes; T lymphocytes; Thy-1.2 antigen; Tumor Cells, Cultured; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.98.4.1740

A deranged expression of MHC class I glycoproteins, characteristic of a variety of malignancies, contributes to the ability of cancer to avoid destruction by T cell-mediated immunity. An abrogation of the metastatic capacity of B16 melanoma cells has been achieved by transfecting an MHC class I-encoding vector into class I-deficient B16 melanoma clones [Gorelik, E., Kim, M., Duty, L. & Galili, U. (1993) Clin. Exp. Metastasis 11, 439-452]. We report here that the deranged expression of class I molecules by B16 melanoma cells is more than a mere acquisition of the capacity to escape immune recognition. Namely, cells of the B16 melanoma prompted splenic lymphocytes to commit death after coculture. However, a class I-expressing and nonmetastatic CL8-2 clone was found to be less potent as an inducer of apoptosis than class I-deficient and metastatic BL9 and BL12 clones. Both Thy1.2+and Thy1.2-splenocytes underwent cell death when exposed to the class I-deficient BL9 clone. A proportion of CD4+and CD8+cells among splenocytes exposed to the BL9 clone was lower than that observed in a coculture with cells of the CL8-2 clone. Consistently, none of the melanoma clones studied produced a ligand to the FAS receptor (FAS-L). Thus, our results provide evidence that (i) the production of FAS-L may not be the sole mechanism by which malignant cells induce apoptosis in immunocytes, and (ii) absence of MHC class I glycoproteins plays an important role in preventing the elimination of potential effector immunocytes by tumor cells.