title: Cervical cancer cells induce apoptosis of cytotoxic T lymphocytes.
abstract: The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.
authors.affiliation: Department of Microbiology, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Contreras
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
authors.forename: R K
authors.initials: RK
authors.lastname: Potkul
authors.forename: P
authors.initials: P
authors.lastname: Bu
authors.forename: J L
authors.initials: JL
authors.lastname: Rossi
authors.forename: A M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: L
authors.initials: L
authors.lastname: Gissmann
authors.forename: L
authors.initials: L
authors.lastname: Qiao
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D015851:Interleukin-7; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor