CCL8 enhances sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages
CCL8 enhances sensitivity of cutaneous squamous cell carcinoma to photodynamic therapy by recruiting M1 macrophages
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CCL8 通过招募 M1 巨噬细胞增强皮肤鳞状细胞癌对光动力治疗的敏感性
DOI：
10.1016/j.pdpdt.2019.03.014
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发表时间：
2019-06-01
影响因子：
3.3
通讯作者：
Wang, Xiuli
中科院分区：
文献类型：
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作者：
Ji, Jie;Wang, Peiru;Wang, Xiuli
背景光动力学疗法（PDT）诱导的抗肿瘤免疫反应被认为依赖于局部和全身炎症的程度。白细胞的募集，特别是趋化因子CCL 8的募集，与炎症反应的启动密切相关。目的：评价CCL 8是否以及如何增强5-氨基乙酰丙酸（ALA）介导的PDT中抗肿瘤的免疫应答。方法：在这项研究中，我们研究了ALA-PDT诱导的CCL 8表达对巨噬细胞募集和极化的影响，Western印迹和Transwell细胞迁移测定。我们在临床皮肤鳞状细胞癌（cSCC）样本、cSCC小鼠模型、肿瘤细胞和巨噬细胞中使用RT-PCR、蛋白质印迹和ELISA评估了ALA-PDT后CCL 8的体外和体内表达。结果：ALA-PDT可增强CCL 8的表达，增加肿瘤中巨噬细胞的数量，并刺激其M1促炎表型，表现为高表达CD 16和CD 80，低表达CD 163，而不表达CD 206。结论：ALA-PDT可诱导CCL 8表达，募集M1巨噬细胞，从而抑制肿瘤生长。
Background Antitumor immunity induced by photodynamic therapy (PDT) is believed to depend on the degree of local and systemic inflammation. The recruitment of leukocytes, in particular by the chemokine CCL8, to the sites of tissue damage has been strongly associated with the initiation of inflammatory reactions.Objective: To evaluate whether and how CCL8 enhances the immune response against tumors in 5-aminolevulinic acid (ALA)-mediated PDT.Methods: In this study, we investigated the effect of ALA-PDT-induced CCL8 expression on the recruitment and polarization of macrophages using immunohistochemistry, western blot and Transwell cell migration assay. We evaluated CCL8 expression following ALA-PDT in vitro and in vivo by using RT-PCR, western blot, and ELISA in clinical cutaneous squamous cell carcinoma (cSCC) samples, a mouse model of cSCC, tumor cells, and macrophages. The effect of the combination of ALA-PDT with CCL8 treatment on anti-tumor immunity was tested in the mouse model.Results: We found that ALA-PDT enhanced CCL8 expression, increased the number of macrophages in tumor, and stimulated their M1 pro-inflammatory phenotype characterized by high expression levels of CD16 and CD80, low expression level of CD163, and absence of CD206 expression. Furthermore, CCL8 enhanced the effect of ALA-PDT on cSCC in mice, such a combination of CCL8 and ALA-PDT had a stronger positive effect in the treatment of mouse cSCC than PDT alone and suppressed tumor volume regrowth.Conclusion: ALA-PDT induces CCL8 expression and recruits M1 macrophages, thus suppressing tumor growth.