, Volume 57, Issue 8, pp 1151-1160
Date: 24 Jan 2008

CD40 ligation in vivo can induce T cell independent antitumor effects even against immunogenic tumors

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Abstract

Antitumor effects of CD40 ligation appear to involve distinct antitumor effector cells in different experimental models. In this study, we tested whether T cells were required for antitumor effects of agonistic anti-CD40 mAb (αCD40) against immunogenic versus poorly immunogenic tumors. Treatment of mice bearing poorly immunogenic B16 melanoma and its more immunogenic variant, B16-hsp72.1, with αCD40 resulted in a similar level of tumor growth suppression. Depletion of T cells did not reduce the antitumor effects in these 2 tumor models. To generate antitumor T cell responses, C57BL/6 mice were immunized with irradiated B16-hsp72.1. Treatment of these vaccinated mice challenged with a high dose of B16-hsp72.1 tumor cells with αCD40 induced tumor growth suppression, which was reduced by T-cell depletion, demonstrating that T cells were involved in the antitumor effect of αCD40. However, immunized mice depleted of T cells and treated with αCD40 were still able to suppress tumor growth as compared to tumor growth in immunized, T cell-depleted mice not treated with αCD40, suggesting that T cells were not required for the antitumor effect of αCD40. To confirm a lack of correlation between tumor immunogenicity and T-cell requirement in antitumor effects of CD40 ligation, we found that αCD40 induced tumor growth suppression in nude and SCID/beige mice bearing highly immunogenic tumors such as Meth A sarcoma, suggesting that macrophages may play a role. Indeed, both poorly immunogenic and highly immunogenic tumors were sensitive to in vitro growth inhibition by macrophages from αCD40-treated mice. Taken together, our results indicate that antitumor effects induced by αCD40, even against immunogenic tumors, can be observed in the absence of T cells and may involve macrophages.

This work was supported by National Institutes of Health Grants CA87025, CA032685, grants from the Midwest Athletes Against Childhood Cancer Fund, and support from the Crawdaddy Foundation.