title: Enhanced induction of very late antigen 4/lymphocyte function-associated antigen 1-dependent T-cell migration to tumor sites following administration of interleukin 12.
abstract: Administration of interleukin 12 (IL-12) into mice bearing CSA1M, OV-HM, Meth A, or MCH-1-A1 tumor induced complete regression of CSA1M and OV-HM tumors but induced only a slight growth inhibition of Meth A and MCH-1-A1 tumors. These effects of IL-12 were associated with high and only marginal levels of T-cell infiltration into CSA1M/OV-HM and Meth A/MCH-1-A1 tumor masses, respectively. Here, we investigated the role of IL-12 in the induction of T-cell migration. Spleen cells from untreated or IL-12-treated CSA1M-bearing mice were stained in vitro with a fluorescein chemical and transferred i.v. into IL-12-untreated CSA1M-bearing mice. Migration of donor cells was quantitated by counting the number of fluorescent cells on cryostat sections of tumor masses. Although only a slight migration was detected for spleen cells from IL-12-untreated CSA1M-bearing as well as IL-12-treated or untreated normal mice, enhanced migration was observed for cells from IL-12-treated CSA1M-bearing mice. A similar enhanced migration was observed for the OV-HM model. In contrast, such an enhancement was only marginal in the Meth A and MCH-1-A1 models. Immunohistochemical studies of tumors from IL-12-treated mice revealed that the predominant T-cell subset was CD4+ in CSA1M and CD8+ in OV-HM tumor masses. Consistent with this observation, the dominant subset of migrating T cells was found to be CD4+ in the CSA1M and CD8+ in the OV-HM models. T-cell migration was inhibited by pretreatment of recipients with either combination of anti-very late antigen 4 + anti-vascular cell adhesion molecule 1 or anti-lymphocyte function-associated antigen 1 + anti-intercellular adhesion molecule 1 monoclonal antibody. These results indicate that IL-12 can confer T cells with a capacity to migrate to tumor sites through very late antigen 4/lymphocyte function-associated antigen 1 adhesion pathways and that the in vivo acquisition of such a capacity following IL-12 treatment correlates with the induction of tumor regression.
authors.affiliation: Biomedical Research Center, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Tsutsui
authors.forename: J P
authors.initials: JP
authors.lastname: Zou
authors.forename: J
authors.initials: J
authors.lastname: Mu
authors.forename: R
authors.initials: R
authors.lastname: Wijesuriya
authors.forename: W G
authors.initials: WG
authors.lastname: Yu
authors.forename: S
authors.initials: S
authors.lastname: Herrmann
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Hamaoka
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12