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• W2155121512 startingPage "5051" @default.
• W2155121512 abstract "Abstract Therapeutic use of IL-2 can generate antitumor immunity; however, a variety of different mechanisms have been reported. We injected IL-2 intratumorally (i.t.) at different stages of growth, using our unique murine model of mesothelioma (AE17; and AE17 transfected with secretory OVA (AE17-sOVA)), and systematically analyzed real-time events as they occurred in vivo. The majority of mice with small tumors when treatment commenced displayed complete tumor regression, remained tumor free for &gt;2 mo, and survived rechallenge with AE17 tumor cells. However, mice with large tumors at the start of treatment failed to respond. Timing experiments showed that IL-2-mediated responses were dependent upon tumor size, not on the duration of disease. Although i.t. IL-2 did not alter tumor Ag presentation in draining lymph nodes, it did enhance a previously primed, endogenous, tumor-specific in vivo CTL response that coincided with regressing tumors. Both CD4+ and CD8+ cells were required for IL-2-mediated tumor eradication, because IL-2 therapy failed in CD4+-depleted, CD8+-depleted, and both CD4+- and CD8+-depleted C57BL/6J animals. Tumor-infiltrating CD8+ T cells, but not CD4+ T cells, increased in association with a marked reduction in tumor-associated vascularity. Destruction of blood vessels required CD8+ T cells, because this did not occur in nude mice or in CD8+-depleted C57BL/6J mice. These results show that repeated doses of i.t. (but not systemic) IL-2 mediates tumor regression via an enhanced endogenous tumor-specific CTL response concomitant with reduced vasculature, thereby demonstrating a novel mechanism for IL-2 activity." @default.
• W2155121512 created "2016-06-24" @default.
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• W2155121512 date "2003-11-15" @default.
• W2155121512 modified "2023-09-30" @default.
• W2155121512 title "IL-2 Intratumoral Immunotherapy Enhances CD8+ T Cells That Mediate Destruction of Tumor Cells and Tumor-Associated Vasculature: A Novel Mechanism for IL-2" @default.
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• W2155121512 doi "https://doi.org/10.4049/jimmunol.171.10.5051" @default.
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