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- W2078438579 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Immune-mediated cancer regression requires tumor infiltration by Ag-specific effector T cells, but lymphocytes are commonly sparse in melanoma metastases. Activated T cells express CXCR3, whose cognate chemokines are CXCL9/MIG, CXCL10/IP-10 and CXCL11/I-TAC. Little is known about expression of these chemokines in lymph node (LN) metastases of melanoma. We evaluated whether metastatic melanoma induces these CXCR3-cognate chemokines in human LN-derived tissues. Also, because these chemokines can be induced by interferon (IFN), we evaluated whether type I or II IFNs (IFN-α or IFN-γ, respectively) can modulate chemokine expression in an in vitro model of the human tumor microenvironment. Production of CXCL9-11 by melanoma-infiltrated nodes (MIN) was no different than tumor-free nodes (TFN); both produced less than activated LN (sentinel immunized nodes, SIN). These data suggest melanoma infiltration into LN neither induces nor reduces CXCL9-11. Stimulation with IFN-α or IFN-γ increased production of CXCL10-11 from MIN, but not TFN or SIN. IFN-γ also increased production of CXCL9 in MIN. In IFN-treated MIN, the primary source of CXCL9-11 was melanoma cells themselves, whereas CD14+ cells were the source of these molecules in SIN. Melanoma cell lines expressed IFN receptors and produced CXCL9-11 in response to IFN treatment. Treatment of melanoma cell lines or primary melanomas in vitro with IFN-γ induced the migration of CXCR3+ T cells in transwell assays, whereas T cell did not significantly migrate in response to resting melanoma cells. Thus, melanoma infiltration of LN is insufficient to induce the production of CXCL9-11, but melanoma may be a significant source of IFN-induced chemokines. Collectively, these data suggest that IFN-α or IFN-γ may act in the tumor microenvironment to increase the chemotactic gradient for CXCR3+ T cells, thus enhancing the capacity of therapeutic vaccines to mediate clinical efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3827." @default.
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- W2078438579 date "2010-04-15" @default.
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- W2078438579 title "Abstract 3827: Interferons induce CXCR3-cognate chemokine production by melanoma" @default.
- W2078438579 doi "https://doi.org/10.1158/1538-7445.am10-3827" @default.
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