title: Amifostine protects lymphocytes during radiotherapy and stimulates expansion of the CD95/Fas and CD31 expressing T-cells, in breast cancer patients.
abstract: A large body of experimental research supports the anti-neoplastic activity of cellular and humoral immunity. Disease and therapy-related immune suppression may be important on the treatment outcome or on the subsequent course of the malignant disease. The aim of the study was to investigate the efficacy of amifostine in preventing the immunological toxicity of post-operative radiotherapy (RT) in breast cancer patients. Using flow-cytometry, we examined comparatively the peripheral blood lymphocytic subpopulations in breast cancer patients undergoing conventional post-operative RT versus a hypofractionated accelerated RT scheme combined with amifostine (HypoARC) administration. Despite the higher radiation dose intensity delivered in the HypoARC group, a significant protection of CD4, CD8, CD19 and CD56 subtypes by amifostine was noted. We further focused on two interesting CD4/CD8 subpopulations involved in cellular apoptosis and trans-endothelial migration, namely the CD95/Fas and CD31 positive lymphocytes. Amifostine protected and induced expansion of these subtypes, which could contribute to the maintenance of a high burden of tumor infiltrating lymphocytes during therapy. It is suggested that amifostine effectively protects lymphocytes against RT, which may enhance the efficacy of the latter. The clinical impact of the CD95(+) and CD31(+) T-cell immunological modulation induced by amifostine requires further investigation.
authors.affiliation: Department of Radiotherapy/Oncology, Microbiology and Internal Medicine/Hematology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Sophia
authors.initials: S
authors.lastname: Ktenidou-Kartali
authors.forename: George
authors.initials: G
authors.lastname: Bourikas
authors.forename: George
authors.initials: G
authors.lastname: Kartalis
authors.forename: Costas
authors.initials: C
authors.lastname: Tsatalas
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D019014:fas Receptor / Q000032:analysis*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011837:Radiation-Protective Agents; D019014:fas Receptor; D004999:Amifostine