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Role of NK and T cells in IL‐12‐induced anti‐tumor response against hepatic colon carcinoma
Author(s) -
PhamNguyen Khiem B.,
Yang Wen,
Saxena Romil,
Thung Swan N.,
Woo Savio L.C.,
Chen ShuHsia
Publication year - 1999
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(19990531)81:5<813::aid-ijc24>3.0.co;2-i
Subject(s) - immune system , cancer research , in vivo , biology , interleukin 12 , immunology , in vitro , cytokine , lymphokine activated killer cell , immunotherapy , adoptive cell transfer , interleukin 21 , cytotoxic t cell , t cell , biochemistry , microbiology and biotechnology
IL‐12 is an immuno‐regulatory cytokine that has been shown to generate a potent NK and Th1 response in a variety of laboratory models. However, the detailed immune development in the hepatic tumor model by IL‐12‐mediated gene therapy has not been clarified. In our previous study, intra‐tumoral transfer of Adv.mIL‐12 (5 × 10 8 pfu) to the MCA26 colon carcinoma liver tumor induced an effective anti‐tumor response, extending the median survival time from 29 to over 54 days, while 25% of the animals became tumor‐free after a single treatment. In this work, we show that NK cells are responsible for the early, and both NK and T cells for the long‐term, Adv.mIL‐12‐induced immune response. Immuno‐histopathological analysis of the tumor and in vitro cytotoxicity study of the mononuclear cells of the liver show that NK cells are the first to infiltrate and mediate tumor cell killing, as early as 48 hr after Adv.mIL‐12 treatment . In vivo and in vitro depletion of these cells completely abolishes this early anti‐tumor response. This activity can be observed in both populations of conventional NK and NKT cells in vitro and in athymic nude mice in vivo. However, the early NK response alone is not sufficient. In vivo T‐cell depletion in both the primary tumor treatment and the long‐term survival re‐challenge study reveals that T cells in addition to NK cells are required in the development of the long‐term survival and immunity attributed to Adv.mIL‐12 gene therapy in this orthotopic tumor model of colon carcinoma. Int. J. Cancer81:813–819, 1999. © 1999 Wiley‐Liss, Inc.