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This Month: Spotlight on Breast Cancer

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Dendritic Cells, Inflammation, and Breast Cancer
The Cancer Journal
FIGURE 1. Pathogenic type 2 cytokine loop in breast cancer. Dendritic cells in breast cancer are exposed to cancer-derived factors—for example, TSLP—that skew their maturation toward expression of OX40L and capacity to activate CD4+ T cells to secrete IL-13 and IL-4, type 2 cytokines. In this environment, responding lymphocytes secreting IL-4 and IL-13 promote tumor development either directly or indirectly via myeloid cells including macrophages. Direct effects include triggering antiapoptotic pathways and steroid metabolism in epithelial cancer cells, as well as promoting stromal fibroblast proliferation and differentiation. Indirect effects include triggering secretion of growth (epidermal growth factor) and proangiogenic (vascular endothelial growth factor) factors by tumor-infiltrating macrophages as well as PDL-1 expression and IL-10 secretion that blunt CD8+ T cell effector function. Cancer cells are likely to also directly activate innate lymphocytes secreting IL-13. The molecular and cellular factors contributing to the global IL-13 production in epithelial cancers likely extend beyond TSLP and are topics of intense study. Another active area is the question of TSLP regulation, whether all breast cancer express it, and at which stages, as well as its role in metastatic niche formation.