title: The mercy of adrenocortical tumor cells on lymphocytes.
abstract: Immunologic escape includes the loss of Fas-receptor and the gain of Fas-ligand expression. Normal adrenal glands express the Fas-receptor and MHC class II molecules in inner cortical zones. A distinctive feature of adrenocortical tumors is the loss of MHC class II expression. Here we demonstrate loss of Fas and gain of Fas-ligand expression in the adrenocortical carcinoma cell line NCI-H295 by immunohistochemistry and RT-PCR. In a co-culture system of tumor cells and HLA-matched leukocytes, CD 8-positive or CD 4-positive lymphocytes, we examined the immunologic escape and the ability to induce apoptosis in the immune cells. The direct co-culture with either leukocytes, CD 8-positive or CD 4-positive lymphocytes reduced spontaneous apoptosis in immune cells from 49.9% to 13.0%, 8.6% and 15.3%, respectively, as determined by FACS analysis of Annexin V binding and LDH release in the medium. In co-culture, cortisol secretion increased up to 200%. Cellular communication does not induce apoptosis in immune cells, but promotes their survival. This may be due to partial HLA class I mismatches contributing to immunologic activity. The viability of the tumor cells was not affected, and these cells were stimulated to secrete cortisol. In summary, immune escape of adrenocortical carcinomas may occur because of altered Fas/Fas-L system expression and loss of MHC class H expression.
authors.affiliation: Department of Internal Medicine, University of Leipzig, Germany.
authors.forename: G W
authors.initials: GW
authors.lastname: Wolkersdörfer
authors.forename: C
authors.initials: C
authors.lastname: Marx
authors.forename: T
authors.initials: T
authors.lastname: Lohmann
authors.forename: S
authors.initials: S
authors.lastname: Brauer
authors.forename: S
authors.initials: S
authors.lastname: Schröder
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Mitsiades
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D006854:Hydrocortisone