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.
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.
Uekusa
Yasuhiro
Y
Department of Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
Gao
Ping
P
Yamaguchi
Nobuya
N
Tomura
Michio
M
Mukai
Takao
T
Nakajima
Chigusa
C
Iwasaki
Masayuki
M
Takeuchi
Noritame
N
Tsujimura
Takahiro
T
Nakazawa
Mitsuhiro
M
Fujiwara
Hiromi
H
Hamaoka
Toshiyuki
T
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
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D018664:Interleukin-12