RRC ID 38970
Author Sumimoto H, Tani K, Nakazaki Y, Tanabe T, Hibino H, Hamada H, Azuma M, Asano S.
Title GM-CSF and B7-1 (CD80) co-stimulatory signals co-operate in the induction of effective anti-tumor immunity in syngeneic mice.
Journal Int J Cancer
Abstract 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-2Kb) expression of LLC/B7 cells with in vitro interferon-gamma 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.
Volume 73(4)
Pages 556-61
Published 1997-11-14
DOI 10.1002/(sici)1097-0215(19971114)73:4<556::aid-ijc17>3.0.co;2-7
PII 10.1002/(SICI)1097-0215(19971114)73:4<556::AID-IJC17>3.0.CO;2-7
PMID 9389572
MeSH Animals Antigens, Neoplasm / metabolism* B7-1 Antigen / genetics B7-1 Antigen / immunology* B7-1 Antigen / metabolism CD4-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / immunology Cancer Vaccines / immunology Cancer Vaccines / radiation effects Carcinoma, Lewis Lung / immunology* Carcinoma, Lewis Lung / metabolism DNA, Complementary / genetics Female Graft Rejection / immunology Granulocyte-Macrophage Colony-Stimulating Factor / genetics Granulocyte-Macrophage Colony-Stimulating Factor / immunology* Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Histocompatibility Antigens Class I / metabolism* Mice Mice, Inbred C57BL Neoplasm Transplantation / immunology Transfection
IF 4.982
Times Cited 27
Human and Animal Cells