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GM‐CSF and B7‐1 (CD80) co‐stimulatory signals co‐operate in the induction of effective anti‐tumor immunity in syngeneic mice
Author(s) -
Sumimoto Hidetoshi,
Tani Kenzaburo,
Nakazaki Yukoh,
Tanabe Tsuyoshi,
Hibino Hitoshi,
Hamada Hirofumi,
Azuma Miyuki,
Asano Shigetaka
Publication year - 1997
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(19971114)73:4<556::aid-ijc17>3.0.co;2-7
Subject(s) - immunity , immunology , cd80 , ratón , cancer research , cellular immunity , immune system , biology , medicine , chemistry , in vitro , genetics , cytotoxic t cell , cd40
B7‐1 (CD80) co‐stimulatory molecule gene–transduced Lewis lung carcinoma (LLC) cells (LLC/B7 cells) resulted in remarkable loss of tumorigenicity in syngeneic C57BL/6 mice (87.5% rejection) compared to B7‐negative, wild‐type LLC (LLC/wt) cells (0% rejection). However, mice that had rejected LLC/B7 cells developed almost no systemic immunity protective against challenge with wild‐type tumor cells after 4 weeks (11.8% rejection). Enhancement of MHC class I (H‐2K b ) expression of LLC/B7 cells with in vitro interferon‐γ treatment did not result in enhancement of protective immunity. In vivo depletion assay revealed that abrogation of tumorigenicity in LLC/B7 depended on CD8 + T cells but not on CD4 + T cells. However, vaccination of C57BL/6 mice with irradiated LLC cells transduced with GM‐CSF (LLC/GM) led to the induction of potent, specific immunity against challenge with the LLC/wt cells after 2 weeks (80.8% rejection). Next, we established a double transfectant of LLC cells expressing both B7‐1 and GM‐CSF (LLC/GM + B7). The tumorigenicity of these clonal cells was also remarkably suppressed (90% rejection) to the same degree as LLC/B7, whereas that of LLC/GM was not suppressed (0% rejection). Interestingly, mice that had rejected LLC/GM+B7 cells developed enhanced protective immunity against challenge with LLC/wt cells after 4 weeks (55.6% rejection) compared to the results of LLC/B7 cells (11.8%). To evaluate whether co‐expression of GM‐CSF and B7‐1 enabled the tumor cells to activate cytotoxic T cells more efficiently than B7‐1 alone, we performed an in vitro killing assay. We found that immunization with LLC/GM+B7 cells resulted in a 3‐fold stronger cytotoxic response than that with LLC/B7. Our data indicate that co‐transfection of the B7‐1 co‐stimulatory molecule and GM‐CSF genes may be more effective for the induction of stronger protective immunity in this experimental system. Int. J. Cancer 73:556–561, 1997. © 1997 Wiley‐Liss, Inc.