巨噬细胞衍生的 CCL22 通过 IL-8 在恶性胸腔积液中促进免疫抑制性肿瘤微环境。
Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion.
机构信息
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, PR China; Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, PR China; Key Laboratory for Tumor Immunology and Biotherapy of Henan Province, Zhengzhou, Henan, 450052, PR China.
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, PR China; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, PR China; Key Laboratory for Tumor Immunology and Biotherapy of Henan Province, Zhengzhou, Henan, 450052, PR China.
出版信息
Cancer Lett. 2019 Jun 28;452:244-253. doi: 10.1016/j.canlet.2019.03.040. Epub 2019 Mar 27.
Immune dysfunction often occurs in malignant pleural effusion (MPE). In our previous study, TGF-β derived predominantly from macrophages plays an important role in impairing T cell cytotoxicity in MPE. Therefore, we aimed to investigate whether other immunoregulatory cells and factors mediated TGF-β secretion from macrophages, involved in the immunosuppressive microenvironment of MPE, and to provide clues for potential immune therapy for MPE as well. We found that CCL22 level in MPE was significantly higher than that in non-malignant pleural effusion. The high level of CCL22 was closely associated with poor survival in MPE patients with lung cancer. CCL22 was dominantly produced by tumor-associated macrophages (TAMs) in MPE. Meanwhile, TAM-derived TGF-β mediated CCL22 expression in TAMs via c-Fos. CCL22 promoted the recruitment of regulatory T cells (Tregs) in MPE. Lastly, Treg-secreted high level of IL-8 further induced TGF-β production from TAMs, and promoted the immunosuppressive tumor microenvironment in MPE. Our results indicate that macrophage-derived CCL22 plays an important role in the immunosuppressive tumor microenvironment via IL-8 in MPE.
免疫功能障碍常发生在恶性胸腔积液（MPE）中。在我们之前的研究中，主要来源于巨噬细胞的 TGF-β 在损害 MPE 中 T 细胞细胞毒性方面发挥重要作用。因此，我们旨在研究其他免疫调节细胞和因子是否通过巨噬细胞分泌 TGF-β，参与 MPE 的免疫抑制微环境，并为 MPE 的潜在免疫治疗提供线索。我们发现，MPE 中的 CCL22 水平明显高于非恶性胸腔积液。高水平的 CCL22 与肺癌 MPE 患者的生存不良密切相关。CCL22 主要由 MPE 中的肿瘤相关巨噬细胞（TAMs）产生。同时，TAM 衍生的 TGF-β 通过 c-Fos 介导 TAMs 中的 CCL22 表达。CCL22 促进 MPE 中调节性 T 细胞（Tregs）的募集。最后，Treg 分泌的高水平 IL-8 进一步诱导 TAMs 产生 TGF-β，并促进 MPE 中的免疫抑制肿瘤微环境。我们的结果表明，巨噬细胞衍生的 CCL22 通过 MPE 中的 IL-8 在免疫抑制性肿瘤微环境中发挥重要作用。
Zotero 插件