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Roles for CCR7 in Cancer Biology

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Chemokine Receptors in Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Since 2001, the association of CCR7 expression by tumor cells with LN metastasis (and associated poor clinical outcome) has been validated in a large number of solid tumors as well as in hematopoietic malignancies. Local factors such as hypoxia, cytokines (endothelins), or epigenetic changes may be involved in the upregulation of CCR7 by tumor cells. Through distinct signaling pathways, activation of CCR7 by its cognate ligands, CCL21 or CCL19, promotes migration, invasion and proliferation of tumor cells in vitro. In addition to responding to exogenous sources of CCR7 ligands, CCR7-expressing tumor cells facilitate their own migration towards CCL21-expressing lymphatics by generating transcellular gradients of CCL19/21. While CCR7 antagonists appear to block LN metastasis in short-term experimental models, the dual roles of CCR7 in protective immunity and tolerance suggests that these agents must be carefully evaluated. Meanwhile, increasing CCR7 expression in DCs may represent a potentially useful means of improving the efficacy of in vivo DC vaccination strategies.

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  1. Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA

    Sam T. Hwang

  2. Dermatology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA

    Lei Fang

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    Fang, L., Hwang, S.T. (2009). Roles for CCR7 in Cancer Biology. In: Fulton, A. (eds) Chemokine Receptors in Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-267-4_6

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