Interleukin-17D promotes lung cancer progression by inducing tumor-associated macrophage infiltration via the p38 MAPK signaling pathway.
Interleukin-17D promotes lung cancer progression by inducing tumor-associated macrophage infiltration via the p38 MAPK signaling pathway.
复制标题
Interleukin-17D 通过 p38 MAPK 信号通路诱导肿瘤相关巨噬细胞浸润，促进肺癌进展
DOI：
10.18632/aging.204208
复制
发表时间：
2022-08-05
期刊：
影响因子：
5.2
通讯作者：
Du, Wei
中科院分区：
文献类型：
--
作者：
Lin, Zhenzhen;Huang, Qiumin;Liu, Junrong;Wang, Hao;Zhang, Xuexi;Zhu, Zhiyan;Zhang, Wei;Wei, Yiliang;Liu, Zhe;Du, Wei
癌症免疫编辑被定义为免疫系统的双重宿主保护和肿瘤促进作用的整合，包括三个阶段：消除、平衡和逃逸。免疫选择压力导致肿瘤细胞失去主要组织相容性复合物表达或获得免疫抑制基因表达，促进肿瘤免疫逃避和肿瘤进展。白细胞介素- 17d （Interleukin-17D, IL-17D）是IL-17细胞因子家族的一员，在宿主防御感染和炎症中起重要作用。然而，IL-17D在肺癌进展中的作用尚不清楚。在本研究中，我们发现IL-17D在人肺癌中高表达，IL-17D表达升高与肿瘤分期和总生存期短有关。IL-17D过表达可显著促进皮下异种移植小鼠模型的肿瘤生长，但对体外细胞增殖仅有轻微影响。通过流式细胞术，我们发现IL-17D过表达增强了肿瘤相关巨噬细胞向肿瘤微环境的募集。基于il17d过表达的A549细胞的表达谱，我们发现IL-17D通过MAPK信号通路增加巨噬细胞极化和招募相关基因的表达水平。此外，抑制p38通路可阻断IL-17D诱导的巨噬细胞浸润。这些结果表明，IL-17D通过p38 MAPK信号通路调节肿瘤免疫微环境，强调IL-17D是肺癌的潜在治疗靶点。
Cancer immunoediting is defined as the integration of the immune system’s dual host-protective and tumor-promoting roles, including three phases: elimination, equilibrium, and escape. Immune selective pressure causes tumor cells to lose major histocompatibility complex expression or acquire immunosuppressive gene expression, which promotes tumor immune evasion and tumor progression. Interleukin-17D (IL-17D), a member of the IL-17 family of cytokines, plays an important role in the host defense against infection and inflammation. However, the role of IL-17D in the progression of lung cancer remains unclear. In this study, we found that IL-17D was highly expressed in human lung cancer, and increased IL-17D expression was associated with tumor stage and short overall survival. IL-17D overexpression significantly promoted tumor growth in subcutaneous xenograft mouse models but only slightly affected cell proliferation in vitro. Using flow cytometry, we found that IL-17D overexpression enhances the recruitment of tumor-associated macrophages to the tumor microenvironment. Based on the expression profile of IL17D–overexpressing A549 cells, we found that IL-17D increased the expression levels of macrophage polarization– and recruitment–related genes through the MAPK signaling pathway. Moreover, inhibition of the p38 pathway blocked macrophage infiltration induced by IL-17D. These results suggest that IL-17D regulates the tumor immune microenvironment via the p38 MAPK signaling pathway, highlighting IL-17D as a potential therapeutic target for lung cancer.
登录
查看更多内容
影响因子：
7.3
作者：
Lee, Younghee;Clinton, Jelita;Chang, Seon Hee
通讯作者：
Chang, Seon Hee
影响因子：
16.6
作者：
Niederst, Matthew J.;Sequist, Lecia V.;Poirier, John T.;Mermel, Craig H.;Lockerman, Elizabeth L.;Garcia, Angel R.;Katayama, Ryohei;Costa, Carlotta;Ross, Kenneth N.;Moran, Teresa;Howe, Emily;Fulton, Linnea E.;Mulvey, Hillary E.;Bernardo, Lindsay A.;Mohamoud, Farhiya;Miyoshi, Norikatsu;VanderLaan, Paul A.;Costa, Daniel B.;Jaenne, Pasi A.;Borger, Darrell R.;Ramaswamy, Sridhar;Shioda, Toshi;Iafrate, Anthony J.;Getz, Gad;Rudin, Charles M.;Mino-Kenudson, Mari;Engelman, Jeffrey A.
通讯作者：
Engelman, Jeffrey A.
Interleukin-17 通过刺激癌细胞中的 COX-2/PGE2 通路间接促进 M2 巨噬细胞分化
影响因子：
4.6
作者：
Li Q;Liu L;Zhang Q;Liu S;Ge D;You Z
通讯作者：
You Z
影响因子：
15.3
作者：
Chen, Xing;Cai, Gang;Li, Xiaoxia
通讯作者：
Li, Xiaoxia
影响因子：
4.7
作者：
HEIL, J;REIFFERSCHEID, G
通讯作者：
REIFFERSCHEID, G