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IL‐12‐ and IL‐2‐induced tumor regression in a new murine model of oral squamous‐cell carcinoma is promoted by expression of the CD80 co‐stimulatory molecule and interferon‐γ
Author(s) -
Thomas Giovana R.,
Chen Zhong,
Enamorado Ileana,
Bancroft Caren,
Van Waes Carter
Publication year - 2000
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(20000501)86:3<368::aid-ijc11>3.0.co;2-1
Subject(s) - cd80 , cytokine , immune system , cancer research , epidermoid carcinoma , immunology , medicine , biology , carcinoma , in vitro , cytotoxic t cell , biochemistry , cd40
Therapy with IL‐12 or IL‐2 induces tumor regression in only a few patients with head‐and‐neck squamous cell carcinoma (SCC), and the factors promoting responsiveness have not been well defined. In this study, we examined whether combined IL‐12 and IL‐2 therapy can induce tumor regression in a new murine model of oral SCC and determined if the anti‐tumor response is promoted by expression of the immune co‐stimulatory molecule CD80 and cytokine IFN‐γ. In CD80‐positive or ‐negative subclones of a BALB/c oral SCC line in syngeneic mice, we showed that systemic rIL‐12 alone was comparable in effectiveness to combined therapy with IL‐12 and peri‐tumoral rIL‐2, inducing complete regression of the CD80 + line B7E11‐4scid. However, therapy with these cytokines had no effect on growth of the CD80 – subclone B7E3‐4scid and did not induce complete regression of the CD80 + subclone B7E11‐4scid in congenic BALB/c IFN‐γ knockout mice, indicating that expression of the CD80 co‐stimulatory molecule and IFN‐γ contributes to tumor regression. In cytokine‐treated mice that rejected the CD80 + SCC line, an increase in infiltrating CD4 + lymphocytes and apoptotic bodies within the tumor specimens was observed, and resistance to rechallenge with the same tumor was detected in 50% of recipients, consistent with an immune response. Our results provide evidence that regression of oral head‐and‐neck SCC may be induced by therapy with systemic IL‐12 and that expression of the CD80 co‐stimulatory molecule by SCC and IFN‐γ by the host promote IL‐12 induced regression of SCC. Int. J. Cancer 86:368–374, 2000. © 2000 Wiley‐Liss, Inc.