Immunotherapeutics Unit, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA.
J Immunol. 2011 May 15;186(10):5656-62. doi: 10.4049/jimmunol.1100463. Epub 2011 Apr 13.
Inflammation is a double-edged sword that can promote or suppress cancer progression. In this study, we report that thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs, is also expressed in human and murine cancers. Our studies with murine cancer cells indicate that TSLP plays an essential role in cancer escape, as its inactivation in cancer cells alone was sufficient to almost completely abrogate cancer progression and lung metastasis. The cancer-promoting activity of TSLP primarily required signaling through the TSLP receptor on CD4(+) T cells, promoting Th2-skewed immune responses and production of immunosuppressive factors such as IL-10 and IL-13. Expression of TSLP therefore may be a useful prognostic marker, and its targeting could have therapeutic potential.
炎症是一把双刃剑,既能促进也能抑制癌症的进展。在这项研究中,我们报告称,胸腺基质淋巴细胞生成素(TSLP)是一种 IL-7 样的 1 型炎症细胞因子,通常与肺部诱导 Th2 型过敏反应有关,它也在人类和鼠类癌症中表达。我们对鼠类癌细胞的研究表明,TSLP 在癌症逃逸中起着至关重要的作用,因为单独在癌细胞中失活 TSLP 就足以几乎完全阻止癌症的进展和肺转移。TSLP 的促癌活性主要需要通过 TSLP 受体在 CD4(+) T 细胞上信号传导来实现,促进 Th2 偏向性免疫反应,并产生免疫抑制因子,如 IL-10 和 IL-13。因此,TSLP 的表达可能是一个有用的预后标志物,其靶向治疗可能具有潜在的治疗作用。