Interleukin-22 promotes tumor angiogenesis
Interleukin-22 promotes tumor angiogenesis
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DOI：
10.1007/s10456-018-9658-x
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发表时间：
2019-05-01
期刊：
影响因子：
9.8
通讯作者：
Ferrara, Napoleone
中科院分区：
文献类型：
--
作者：
Protopsaltis, Nicholas J.;Liang, Wei;Ferrara, Napoleone
T（H）17细胞在癌症的发生和发展中起着重要而复杂的作用。我们先前报道了T（H）17细胞和IL-17通过诱导免疫抑制和促血管生成骨髓细胞募集到肿瘤微环境来介导抗VEGF治疗的抗性。在这里，我们证明了IL-22，T（H）17细胞表达的关键效应细胞因子，直接作用于内皮细胞，以促进肿瘤血管生成。IL-22在体外诱导内皮细胞增殖、存活和趋化性以及在离体小鼠脉络膜外植体模型中诱导新血管形成。用中和抗体阻断IL-22可显著抑制与微血管密度降低相关的肿瘤生长。未观察到IL-22与VEGF的协同作用。这些结果将IL-22鉴定为阻断肿瘤血管生成的潜在治疗靶点。
T(H)17 cells play important yet complex roles in cancer development and progression. We previously reported that T(H)17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by T(H)17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody, significantly inhibits tumor growth associated with reduced microvascular density. No synergistic effect of IL-22 with VEGF was observed. These results identify IL-22 as a potential therapeutic target for blocking tumor angiogenesis.