Yuan Ming, Zhu Ha, Xu Junfang, Zheng Yuanyuan, Cao Xuetao, Liu Qiuyan
National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
J Immunol Res. 2016;2016:6530410. doi: 10.1155/2016/6530410. Epub 2016 Jun 29.
Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs) play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4(+) and CD8(+) T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth.
中性粒细胞在炎症过程中发挥传统作用,是抵御感染的第一道防线。尽管它们对肿瘤发生和进展的作用仍存在争议,但最近越来越多的证据表明,肿瘤相关中性粒细胞(TANs)在癌症生物学的多个方面发挥关键作用。在此,我们检测到3LL荷瘤小鼠血清中的趋化因子CXCL1显著升高。在体外,3LL细胞组成性表达并分泌更高水平的CXCL1。此外,敲低3LL细胞中CXCL1的表达可通过抑制外周血中性粒细胞募集到肿瘤组织中,显著阻碍肿瘤生长。此外,肿瘤浸润的中性粒细胞表达更高水平的髓过氧化物酶(MPO)和Fas/FasL,这可能参与TAN介导的对CD4(+)和CD8(+) T细胞的抑制。这些结果表明,肿瘤来源的CXCL1有助于TANs浸润肺癌,促进肿瘤生长。