Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287, USA.
Cancer Cell. 2013 Nov 11;24(5):631-44. doi: 10.1016/j.ccr.2013.10.009.
A large body of evidence indicates that chronic inflammation is one of several key risk factors for cancer initiation, progression, and metastasis. However, the underlying mechanisms responsible for the contribution of inflammation and inflammatory mediators to cancer remain elusive. Here, we present genetic evidence that loss of CXCR2 dramatically suppresses chronic colonic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid-derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis-associated cancer. CXCR2 ligands were elevated in inflamed colonic mucosa and tumors and induced MDSC chemotaxis. Adoptive transfer of wild-type MDSCs into Cxcr2(-/-) mice restored AOM/DSS-induced tumor progression. MDSCs accelerated tumor growth by inhibiting CD8(+) T cell cytotoxic activity.
大量证据表明，慢性炎症是癌症发生、发展和转移的几个关键风险因素之一。然而，炎症和炎症介质促进癌症发生的潜在机制仍不清楚。在这里，我们提供遗传证据表明，CXCR2 的缺失通过抑制髓系来源的抑制细胞（MDSCs）浸润结肠黏膜和结肠炎相关癌症小鼠模型中的肿瘤，显著抑制慢性结肠炎症和结肠炎相关肿瘤发生。CXCR2 配体在炎症性结肠黏膜和肿瘤中升高，并诱导 MDSC 趋化性。将野生型 MDSC 过继转移到 Cxcr2(-/-) 小鼠中，恢复了 AOM/DSS 诱导的肿瘤进展。MDSC 通过抑制 CD8(+) T 细胞细胞毒性活性加速肿瘤生长。
