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

J Leukoc Biol. 2002 Nov;72(5):864-73.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Division
  • Cell Movement*
  • Female
  • Graft Rejection / immunology
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / genetics
  • Interleukin-12 / physiology*
  • Kinetics
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • RNA, Messenger / biosynthesis
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • RNA, Messenger
  • Interleukin-12