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.