Oncoimmunology:浙江大学王青青研究组揭示白细胞介素对肠炎相关肿

摘要 : 近日，国际学术期刊《OncoImmunology》在线发表了浙江大学基础医学院王青青教授课题组题为“Protective function of interleukin-27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells”的研究论文。

近日，国际学术期刊《OncoImmunology》在线发表了浙江大学基础医学院王青青教授课题组题为“Protective function of interleukin-27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells”的研究论文。研究发现在肠炎相关的肠癌模型中，白细胞介素27可以抑制肠上皮细胞中促炎因子的表达，从而减少促肿瘤的髓系抑制性细胞(Myeloid-derived suppressor cells, MDSCs)在肠道固有层中的聚集，最终起到抑制肿瘤生长的作用。博士生崔碧珺为论文第一作者，王青青教授为通讯作者。

以往研究表明，慢性炎症对肿瘤的产生有促进作用，由克罗恩氏病和溃疡性结肠炎导致的肠癌是典型的炎症相关的肿瘤。白细胞介素27(Interleukin-27, IL-27)已经被证明在炎症相关疾病中表达上升，并且起到重要的调节作用。但是目前对IL-27在肠炎中的作用尚有争议，而肠炎相关肿瘤模型中并未有相关报道。该研究阐明了IL-27在肠炎相关肿瘤模型中的保护作用，这种保护作用是通过抑制肠道上皮细胞产生的促炎因子导致的。在AOM/DSS诱导的模型中，IL-27受体(WSX-1)敲除小鼠有更高的肠道肿瘤载量，更活跃的细胞分裂，更多促肿瘤生长的MDSCs在肠道固有层中聚集。进一步研究表明，肠上皮来源的IL-6，GM-CSF，CXCL，TNF-α等被Toll样受体所激活后分泌的促炎因子在WSX-1敲除小鼠中表达升高，并且体外实验也证明了肠上皮细胞来源的这些细胞因子对MDSCs的趋化作用。因此IL-27抑制了上皮细胞分泌的细胞因子，从而减轻了MDSCs的聚集，对肠癌起到抑制作用。

该研究首次揭示了IL-27对肠炎相关肿瘤的作用，为炎症和癌症的研究提供了新的线索，抗肿瘤免疫提供了新的思路。

原文链接：

Protective function of interleukin-27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial Cells

原文摘要：

Numerous studies have demonstrated that inflammation contributes to a variety ofcancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinalinflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC throughsuppression of inflammatory cytokines in intestinal epithelial cells (IECs). IL-27Rα (WSX-1) deficiency promotes the CAC development in mice, which is driven by enhanced tumor cell proliferation, more intensive myeloid-derived suppressor cells(MDSC) accumulation in colon lamina propria and higher level of inflammatorycytokines and chemokines in IECs. The levels of IL-6, TNF-α, GM-CSF and CXCL1 triggered in vitro by toll-like receptor ligands are significantly upregulated in IECs from WSX-1 KO mice. Removal of commensal microorganism through antibiotic treatment in mice to eliminate TLR ligands deprives the protective function of IL-27on CAC tumor growth. Thus, IL-27 suppresses CAC formation through an anti-inflammation mechanism targeting IECs and in turn resists the tumorigenesis. Hence, our study explained how IL-27 exerts its anti-inflammatory function on epithelial cells to fight against chronic-inflammation-associated cancer, which might provide new insights on the potential therapeutic strategies for cancer.

doi:10.1080/2162402X.2016.1268309

作者：王青青

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