title: Interleukin-12 requires initial CD80-mediated T-cell activation to support immune responses toward human breast and ovarian carcinoma.
abstract: One possible reason for the poor immunogenicity of tumors is the induction of peripheral tolerance by tumor cells that fail to deliver costimulatory signals. Furthermore, T cells stimulated with wild-type tumor cells often fail to secrete cytokines. The present study has been undertaken to identify cytokines that cooperate with CD80 in T-cell activation in vitro toward human breast and ovarian carcinoma cell lines. Tumor cell-mediated T-lymphocyte activation was analyzed directly in allogeneic mixed lymphocyte/tumor cell cultures as proliferation and effector functions were assessed in cytotoxic T-cell assays. Interleukin-7 (IL-7) amplified the proliferative response toward CD80-transfected breast and ovarian carcinomas and stimulated predominantly CD4+ T lymphocytes. IL-12 represses the proliferative response of naive T cells but cooperates with CD80-mediated activation during secondary stimulations. In long-term T-cell cultures, IL-12 synergizes with CD80 expression to stimulate cytolytic CD8+ T-cell lines, which recognize a breast carcinoma line in a human histocompatibility leukocyte antigen-restricted manner. These studies illustrate that costimulation is necessary for tumor cells to function as alloantigen-presenting cells. Furthermore, when added after the priming of T cells with CD80-transfected tumor cells, IL-12 could be helpful in propagating sufficient T-cell numbers to be used in adoptive transfers during cellular immunotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tübingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Gückel
authors.forename: G C
authors.initials: GC
authors.lastname: Meyer
authors.forename: W
authors.initials: W
authors.lastname: Rudy
authors.forename: R
authors.initials: R
authors.lastname: Batrla
authors.forename: S C
authors.initials: SC
authors.lastname: Meuer
authors.forename: G
authors.initials: G
authors.lastname: Bastert
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
authors.forename: U
authors.initials: U
authors.lastname: Moebius
mesh_terms: D018122:B7-1 Antigen / Q000235:genetics*; D001943:Breast Neoplasms / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics*; D015851:Interleukin-7 / Q000235:genetics; D007700:Kinetics; D010051:Ovarian Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D018122:B7-1 Antigen; D015851:Interleukin-7; D018664:Interleukin-12