Department of Basic Sciences, Georgia Campus - Philadelphia College of Osteopathic Medicine, Suwanee, Georgia, USA.
Clin Exp Immunol. 2012 May;168(2):192-9. doi: 10.1111/j.1365-2249.2012.04570.x.
Interleukin (IL)-22 is a cytokine involved in inflammatory and wound healing processes that is secreted primarily by T helper type 17 (Th17) cells. IL-22 receptor (IL-22R) expression is limited to epithelial cells of the digestive organs, respiratory tract and skin. Most tumours originating in these sites over-express IL-22R. Interestingly, there is an increase in Th17 frequency within the peripheral blood and tumour microenvironment of advanced cancer patients. Subsequently, IL-17 has been shown to display both pro-tumour and anti-tumour functions. Because many tumours lack expression of the IL-17 receptor, the effects of IL-17 on tumour growth are generated by cells that surround the tumour cells. Like IL-17, high levels of IL-22 have been detected in tumour tissues and the peripheral blood of cancer patients; however, the direct effect of IL-22 on tumour cells has remained largely unknown. In this report, we show that IL-22 stimulated production of vascular endothelial growth factor (VEGF) and the anti-apoptotic factor Bcl-X(L) in IL-22R-positive HPAFII human pancreatic cancer cells. Additionally, IL-22 augmented HPAFII cell production of immunosuppressive cytokines. We show further that IL-22 activation of HPAFII cells diminished T cell production of interferon (IFN)-γ through the action of IL-10. Strikingly, we show for the first time that IL-22 can fully protect cancer cells from natural killer (NK) cell-mediated cytotoxicity by stimulating tumour production of IL-10 and transforming growth factor (TGF)-β1. Our data support the idea that IL-22 may act to promote the pathogenesis of cancers rather than function in anti-tumour immunity.
白细胞介素 (IL)-22 是一种参与炎症和伤口愈合过程的细胞因子，主要由辅助性 T 细胞 17（Th17）细胞分泌。IL-22 受体（IL-22R）的表达仅限于消化器官、呼吸道和皮肤的上皮细胞。大多数起源于这些部位的肿瘤过度表达 IL-22R。有趣的是，晚期癌症患者外周血和肿瘤微环境中 Th17 频率增加。随后，IL-17 已被证明具有促肿瘤和抗肿瘤功能。由于许多肿瘤缺乏 IL-17 受体的表达，IL-17 对肿瘤生长的影响是由肿瘤细胞周围的细胞产生的。与 IL-17 一样，高水平的 IL-22 已在肿瘤组织和癌症患者的外周血中检测到；然而，IL-22 对肿瘤细胞的直接影响在很大程度上仍然未知。在本报告中，我们表明 IL-22 刺激了 IL-22R 阳性 HPAFII 人胰腺癌细胞中血管内皮生长因子 (VEGF) 和抗凋亡因子 Bcl-X(L) 的产生。此外，IL-22 增强了 HPAFII 细胞产生免疫抑制细胞因子的能力。我们进一步表明，IL-22 通过 IL-10 的作用激活 HPAFII 细胞会减少 T 细胞产生干扰素 (IFN)-γ。引人注目的是，我们首次表明 IL-22 可以通过刺激肿瘤产生 IL-10 和转化生长因子 (TGF)-β1 来完全保护癌细胞免受自然杀伤 (NK) 细胞介导的细胞毒性。我们的数据支持这样一种观点，即 IL-22 可能通过促进癌症的发病机制而不是通过抗肿瘤免疫来发挥作用。
