B7-1, IFN gamma and anti-CTLA-4 co-operate to prevent T-cell tolerization during immunotherapy against a murine T-lymphoma.

We previously reported on a murine T lymphoma cell line, BW-Sp3, with inherent immunogenicity. BW-Sp3 tumors can elicit an anti-tumor CD8(+) CTL response capable of mediating a regression of subcutaneous tumors. However, this immune response is inadequate to eliminate cancer cells completely in a significant percentage of the recipients, resulting in progressing tumors. In this tumor model, tumor progression correlated with a tolerization of tumor-reactive T cells and cellular immunotherapy of tumor bearing animals, with or without B7-mediated costimulation, even increased tumor progression (Raes et al, 1998). In the present study, we investigated whether the co-expression of IFN gamma, together with B7-1, could have beneficial effects on immunotherapy. Although immunotherapy with IFN gamma and B7-1 single transfectants tended to tolerize anti-tumor T-cells and consequently increased tumor growth, the B7-1/IFN gamma double transfectants resulted in a more beneficial outcome. This phenomenon correlated with an increased CTL-inducing potential of the double transfectants. Secondly, we wondered whether CTLA-4 signalling was involved in the down-regulation of the anti-tumor response. Indeed, when immunotherapy was provided along with anti-CTLA-4, the protection by B71/IFN gamma double transfectants was further improved and the tumor-promoting effect of BW-Sp3(B7-1) was compensated for. Our results indicate that B7-1, IFN gamma and the blockade of CTLA-4 cooperate to tilt the balance in favour of tumor elimination, while either factor alone fails to do so or even promotes tumor growth.

Van Ginderachter JA ，Liu Y ，Geldhof AB ，Brijs L ，Thielemans K ，De Baetselier P ，Raes G ... -  《INTERNATIONAL JOURNAL OF CANCER》

Active antitumor immunotherapy, with or without B7-mediated costimulation, increases tumor progression in an immunogenic murine T cell lymphoma model.

Raes G ，Van Ginderachter J ，Liu YQ ，Brys L ，Thielemans K ，De Baetselier P ，Geldhof A ... -  《-》

Tumor rejection requires a CTLA4 ligand provided by the host or expressed on the tumor: superiority of B7-1 over B7-2 for active tumor immunization.

Gajewski TF ，Fallarino F ，Uyttenhove C ，Boon T ... -  《JOURNAL OF IMMUNOLOGY》

Intrinsic and extrinsic manipulation of B7/CTLA-4 interaction for induction of anti-tumor immunity against osteosarcoma cells.

Nagamori M ，Kawaguchi S ，Murakami M ，Wada T ，Nagoya S ，Yamashita T ，Inobe M ，Uede T ... -  《ANTICANCER RESEARCH》

B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor system in vitro.

Gajewski TF 《JOURNAL OF IMMUNOLOGY》