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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
Author(s) -
Harada Mamoru,
Tamada Koji,
Abe Koichiro,
Li Tieli,
Onoe Yasuhiro,
Tada Hitoshi,
Takenoyama Mitsuhiro,
Yasumoto Kosei,
Kimura Genki,
Nomoto Kikuo
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980130)75:3<400::aid-ijc13>3.0.co;2-c
Subject(s) - melanoma , medicine , lymph , systemic administration , lymph node , primary tumor , pathology , cancer , immunology , cancer research , metastasis , in vivo , biology , microbiology and biotechnology
We investigated the effect of the systemic administration of interleukin (IL)‐12 on the anti‐tumor potential of tumor‐draining 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 μg) 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 μg) 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. Int. J. Cancer 75:400–405, 1998. © 1998 Wiley‐Liss, Inc.