1. CD8+ depletion and IFN-γ–deficient myeloid cells and lung metastasis inhibition in Tgfbr2MyeKO mice.
CD8+ depletion and IFN-γ–deficient myeloid cells and lung metastasis inhibition in Tgfbr2MyeKO mice. A, flow cytometry shows significantly decreased CD8+ T cells in Tgfbr2MyeKO mice after receiving injection of CD8 neutralizing antibody. B, CD8 neutralizing antibody significantly decreased lung metastasis in Tgfbr2MyeKO mice. All data are represented as mean ± SEM. ***, P < C, schematic hypotheses for mechanisms underlying decreased metastasis in the Tgfbr2MyeKO mice. TGF-β1 production is enhanced in myeloid cells through autocrine (TGF-β1 produced in CD11b+Ly6G+ cells) and/or paracrine mechanisms (TGF-β1 from tumor cells or other cells, such as CD4+, Tregs, or stromal fibroblasts). Deletion of Tgfbr2 in myeloid cells decreased the production of type II cytokines, TGF-β1, as well as arginase 1 and iNOS, which in turn increased IFN-γ expression in CD8+ T cells. This likely improves systemic immune surveillance and results in decreased lung metastasis in the Tgfbr2MyeKO mice. In the metastatic lung, deletion of Tgfbr2 also enhances IFN-γ production in a subset of macrophages and neutrophils, and functional maturation of dendritic cells, which may improve local innate immunity. APC, antigen-presenting cells.
Yanli Pang et al. Cancer Discovery 2013;3:
©2013 by American Association for Cancer Research