Systemic administration of interleukin-12 can restore the anti-tumor potential of B16 melanoma-draining lymph node cells impaired at a late tumor-bearing state
✍ Scribed by Mamoru Harada; Koji Tamada; Koichiro Abe; Tieli Li; Yasuhiro Onoe; Hitoshi Tada; Mitsuhiro Takenoyama; Kosei Yasumoto; Genki Kimura; Kikuo Nomoto
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 100 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We investigated the effect of the systemic administration of interleukin (IL)-12 on the anti-tumor potential of tumordraining lymph nodes (LNs). Tumor-draining LN cells on day 10 after s.c. inoculation of B16 melanoma showed a significant anti-tumor effect against established pulmonary metastases after in vitro expansion, whereas those on either day 20 or 30 exhibited an impaired anti-tumor potential. However, i.p. injections of IL-12 (0.5 g) on days 18, 20 and 22 significantly increased the total number of tumor-draining LN cells on day 24 and, furthermore, restored their anti-tumor potential after in vitro expansion. In addition, i.p. injection of IL-12 (0.1 g) on days 20, 22, 24, 26 and 28 significantly suppressed the growth of s.c.-inoculated B16 melanoma and finally cured the tumors in 6 of 12 mice (50%), whereas dissection of the tumor-draining LNs on day 18, prior to the IL-12 treatment, decreased both the IL-12-induced anti-tumor effect and the percentage of cured mice (8.3%). Cured mice acquired a specific protective immunity. Collectively, our results indicate that the systemic administration of IL-12 can restore the immunotherapeutic potential of tumor-draining LNs, which was impaired at the late tumor-bearing state, and that the IL-12-induced systemic anti-tumor activity is preceded by the restoration of an anti-tumor response in tumor-draining LNs.