The TLR7/8 agonist R848 optimizes host and tumor immunity to improve therapeutic efficacy in murine lung cancer

作者全名："Zhou, Jianchun; Xu, Yu; Wang, Guansong; Mei, Tonghua; Yang, Hao; Liu, Yuliang"

作者地址："[Zhou, Jianchun; Mei, Tonghua; Yang, Hao; Liu, Yuliang] Chongqing Med Univ, Affiliated Hosp 1, Resp Med Dept, Chongqing 400016, Peoples R China; [Xu, Yu; Wang, Guansong] Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China; [Liu, Yuliang] Chongqing Med Univ, Affiliated Hosp 1, Resp Med Dept, 1 Med Coll Rd, Chongqing 400016, Peoples R China"

通信作者："Liu, YL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Resp Med Dept, Chongqing 400016, Peoples R China.; Liu, YL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Resp Med Dept, 1 Med Coll Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000806070000001

JCR分区：Q2

影响因子：5.2

年份：2022

卷号：61

期号：1

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结束页：　

文献类型：Article

关键词：resiquimod; Toll-like receptor 7; lung cancer; tumor microenvironment; immune cells; immunity

摘要："Treatment with the Toll-like receptor 7 (TLR7) agonist, resiquimod (R848), is effective in various types of cancer, such as breast, pancreatic and colorectal cancer. The reported antitumor effect of R848 in lung cancer is considered to be achieved by targeting macrophages. In the present study, it was demonstrated that TLR7 expression on various immune cell types initially rises, then declines in the late stage of lung cancer. Intraperitoneal injection of R848 resulted in a reduction in tumor burden and prolonged survival in both subcutaneous and metastatic lung cancer models in C57BL/6 mice. Initial treatment with R848 at an early stage was found to be the optimal choice. Systemic injection of R848 promoted the activation of innate and adaptive immune responses. Systemic administration of R848 upregulated TLR7 expression in dendritic cells (DCs) and enhanced the activation of DCs and natural killer (NK) cells. Moreover, this treatment also resulted in increased production of T helper cell-associated cytokines in serum, including IFN-gamma, TNF-alpha and IL-2. In addition, continuous treatment with R848 increased the proportion of DCs, NK and CD8(+) T cells, and reduced that of Foxp3(+) regulatory T cells in the tumor microenvironment. These findings supported the use of R848 treatment for lung cancer via TLR7 targeting and provided insight into the underlying therapeutic mechanism."

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