title: A role for endogenous IL-12 in tumor immunity: IL-12 is required for the acquisition of tumor-migratory capacity by T cells and the development of T cell-accepting capacity in tumor masses.
abstract: Interleukin (IL)-12 plays a central role in the initiation and regulation of T cell-mediated immune responses. The present study investigated how IL-12, endogenously produced during tumor vaccination, functions for anti-tumor immune responses. Mice were given anti-IL-12 monoclonal antibody during immunization with attenuated syngeneic tumor cells. Splenic T cells from anti-IL-12-treated immunized mice exhibited comparable levels of tumor-neutralizing activity with those from tumor-immunized mice without anti-IL-12 treatment. When these two groups of mice were directly challenged with viable tumor cells, tumor rejection was induced only in anti-IL-12-untreated mice. T cell infiltration was observed at the site of tumor challenge in these mice, whereas such a T cell infiltration did not occur in anti-IL-12-treated mice. The tumor-migratory capacity was directly assessed by transferring spleen cells from tumor-immunized mice into syngeneic, tumor-bearing recipient mice and by quantitating donor cells migrating into recipients' tumor masses. T cells from anti-IL-12-treated tumor-immunized mice were found to exhibit a markedly reduced tumor-migratory capacity when compared with that of anti-IL-12-untreated mice. Moreover, the migration of T cells from anti-IL-12-untreated mice to tumor masses prepared in anti-IL-12-treated mice was severely reduced. These results indicate that endogenously produced IL-12 has dual roles in anti-tumor-immune resistance: One is to confer T cells with a tumor-migratory capacity, and the other is to allow tumor masses to develop the capacity to accept tumor-migrating T cells.
authors.affiliation: Department of Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uekusa
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Nobuya
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.forename: Takao
authors.initials: T
authors.lastname: Mukai
authors.forename: Chigusa
authors.initials: C
authors.lastname: Nakajima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Noritame
authors.initials: N
authors.lastname: Takeuchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hamaoka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018664:Interleukin-12