title: Gamma-radiation upregulates MHC class I/II and ICAM-I molecules in multiple myeloma cell lines and primary tumors.
abstract: The gamma-irradiation of normal cells causes an increased synthesis of specific proteins. However, few studies have described the effects of high doses of irradiation on the expression of cell surface antigens in tumor cells. This study analyzed the effects of high doses of gamma-irradiation on the surface antigen expression of Major Histocompatability Complex (MHC) class I/II and intercellular adhesion molecule-1 (ICAM-I) in human multiple myeloma (MM) cell lines ARP-1, ARK-RS, and 10 MM primary tumors. The expression of surface antigens was evaluated by fluorescence-activated cell sorter analysis at different time points, following the exposure to high doses of gamma-irradiation. Doses of 10,000 and 15,000 cGy were not sufficient to totally block cell replication in both cell lines and primary tumors; cell replication was able to be inhibited completely only at 18,000 cGy. Lower doses (10,000 cGy) and lethal doses of irradiation (i.e., 15,000 and 18,000 cGy) increased the expression of all surface antigens present on the cells before irradiation. Essentially, such upregulation was shown to be dose dependent, with higher radiation doses resulting in higher antigen expression. Furthermore, when the kinetics of this upregulation were studied 3 and 6 d after irradiation, there was a constant increase in antigen expression in MM cells. These findings suggest that upregulation of costimulatory molecules, such as of MHC class I/II antigens and ICAM-I molecules in MM patients treated by gamma-radiation, can increase the immunogenicity of the tumor cells. In light of these findings, radiotherapy combined with immunotherapy might be considered in relapsing patients after receiving the standard treatment.
authors.affiliation: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6591, USA. maurizio.chiriva@ttuhsc.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
authors.forename: Fabio
authors.initials: F
authors.lastname: Grizzi
authors.forename: Justin
authors.initials: J
authors.lastname: Pinkston
authors.forename: K John
authors.initials: KJ
authors.lastname: Morrow
authors.forename: Nicholas
authors.initials: N
authors.lastname: D'Cunha
authors.forename: Eldo E
authors.initials: EE
authors.lastname: Frezza
authors.forename: Pier Carlo
authors.initials: PC
authors.lastname: Muzzio
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006680:HLA Antigens; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006680:HLA Antigens; D018799:Intercellular Adhesion Molecule-1