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(Journal of Leukocyte Biology. 2002;72:864-873.)
© 2002 by Society for Leukocyte Biology

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

Yasuhiro Uekusa^*, Ping Gao^*, Nobuya Yamaguchi^*, Michio Tomura^*, Takao Mukai^*, Chigusa Nakajima^*, Masayuki Iwasaki^*, Noritame Takeuchi^*, Takahiro Tsujimura, Mitsuhiro Nakazawa, Hiromi Fujiwara^* and Toshiyuki Hamaoka^*

^* Department of Oncology, Osaka University Graduate School of Medicine, and
Second Department of Oral and Maxillo-Facial Surgery, Osaka University Faculty of Dentistry, Osaka University, Suita, Japan; and
Department of Pathology, Sumitomo Hospital, Osaka, Japan

Correspondence: Dr. Hiromi Fujiwara, Department of Oncology (C6), Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail: hf{at}ongene.med.osaka-u.ac.jp

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.

Key Words: T cell migration • interleukin (IL)-12 • tumor immunity

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