COX-2 blockade immunologically suppresses brain metastasis of lung cancer

非甾体类抗炎药的常规使用与降低人类癌症风险之间的关系已被证实。NSAID作为考克斯-2抑制剂发挥作用，可阻止PGE 2的产生，PGE 2可诱导荷癌宿主中的MDSC。因此，我们假设，考克斯-2阻断剂将通过抑制MDSC的发展及其在肿瘤微环境（TME）中的趋化因子介导的积累来抑制癌症的脑转移。在小鼠和人脑转移病例中，与周围或正常脑相比，肿瘤组织中考克斯-2和CCL 2（一种主要吸引MDSC的趋化因子）的表达水平增加。同时，在肿瘤组织中观察到高水平的MDSC浸润。在使用LL/2鼠肺癌细胞系的小鼠脑肿瘤模型中，用NSAID治疗抑制脑转移形成，同时抑制MDSC。我们的研究结果表明，考克斯-2途径促进脑转移的肺癌的发展和积累的MDSC。

Associations between the regular use of NSAIDs and reduced cancer risks in human have been shonw. NSAIDs function as COX-2 inhibitors that prevent the production of PGE2, which induces MDSCs in cancer-bearing hosts. We thus hypothesized that COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and their chemokine-mediated accumulation in the tumor microenvironment (TME). In both mouse and human brain metastasis cases, the expression levels of COX-2 and CCL2, a chemokine primarily attracting MDSCs, were increased in the tumor tissues compared with the periphery or normal brain. Concomitantly, the infiltration of MDSCs was observed at high levels in the tumor tissues. In the mouse brain tumor models using LL/2 murine lung cancer cell line, treatment with NSAIDs inhibited brain metastasis formation with the suppression of MDSCs. Our findings show that the COX-2 pathway promotes brain metastases of lung cancers by development and accumulation of MDSCs.