CD11b regulates immunity to tumor and mediates tumor promotion of macrophages recruited by mesenchymal stem cells (TUM4P.922)

Abstract

Abstract Here we report that systemic gadolinium chloride, or GdCl3, treatment, a potent macrophage inhibitor, significantly suppressed melanoma development in mice, which was related to the reduction of CD11b expression. We then directly examined the role of CD11b in tumorigenesis in mice by using CD11b-/- mice, or by blocking CD11b function with anti-CD11b antibody. We found that knockout or blockage of CD11b significantly suppressed the development of melanoma. Histological analysis of melanoma tissue demonstrated that abundant inflammatory cells infiltrated the surrounding region of tumor in CD11b-/- mice but not in wild type mice. This result is consistent with the increased expression of inflammatory cytokines, including TNFα, IL-6, IL-12 and IL-23, in GdCl3-treated macrophages in vitro. More IL-17 was produced in CD4+ T cells co-cultured with GdCl3-treated macrophages compared with no GdCl3 treatment, and administration of a low amount of IL-17 suppressed melanoma growth in mice in vivo, showing that CD11b-mediated immune tolerance in tumor may be through inhibition of IL-17 production in T cells. Furthermore, we reported that tumor-educated or TNFα-pretreated mesenchymal stem cells promoted tumor development by recruiting macrophages, thus we examined the effect of GdCl3 treatment or CD11b knockout and found that the tumor promoting effect was abolished. Therefore, our findings demonstrate that CD11b provides a tolerogenic signal during the immune response to tumor.