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Metastatic disease and its associated complications are responsible for the vast majority of cancer-related deaths. In the metastatic process, immune cells function paradoxically: some cells prevent metastasis while other cells promote metastasis. Recently, we showed how distinct immune cell subsets cooperate to support breast cancer metastasis through suppression of other anti-metastatic immune cells. This cooperation occurred between gamma-delta (γδ) T cells and neutrophils to inhibit cytotoxic T-lymphocytes. γδ T cells are a rare population of cells that express a T cell receptor, function like innate immune cells and reside in mucosal tissues. Although we defined the role of γδ T cells in breast cancer metastasis, their function during metastasis of other cancer types is entirely unknown. As such, the goal of this proposal is to provide insight into the role of these cells during colorectal cancer metastasis. This goal will be accomplished by using a novel, spontaneous metastasis model of colorectal cancer metastasis. The data generated from these experiments will improve our understanding of basic metastasis biology and γδ T cell biology, as well as uncover potential immunotherapeutic approaches for patients with metastatic disease.
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