CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages

Department of Pathology, University of California, San Francisco, CA 94143, USA.
Cancer cell (Impact Factor: 23.52). 09/2009; 16(2):91-102. DOI: 10.1016/j.ccr.2009.06.018
Source: PubMed


During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4(+) T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b(+)Gr1(-)F4/80(+) macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.

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Available from: Nikita Kolhatkar
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    • "In contrast, breast tumor models are characterized by a Th2 bias (Czarneski et al., 2001; Jensen et al., 2003). Our observation of increased branching in Th2-organoid co-cultures echoes the observation of Th2 cells dominating mammary adenocarcinomas and promoting invasion as well as pulmonary metastasis (DeNardo et al., 2009). In fact, numerous findings in cancer research imply that survival and differentiation of mammary epithelial cells that form tumors are indeed regulated by a delicate balance between Th1/Th2 signaling. "
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