The role of MHC class I glycoproteins in the regulation of induction of cell death in immunocytes by malignant melanoma cells.
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.
Fishman
D
D
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, B.G.U. Cancer Research Center, P.O. Box 653, Beer-Sheva 84105, Israel.
Irena
B
B
Kellman-Pressman
S
S
Karas
M
M
Segal
S
S
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053222:Fas Ligand Protein; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006023:Glycoproteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins