Open AccessThe TLR7/8 agonist R848 optimizes host and tumor immunity to improve therapeutic efficacy in murine lung cancer
Author(s) -
Jianchun Zhou,
Yü Xu,
Guansong Wang,
Tonghua Mei,
Hao Yang,
Yuliang Liu
Publication year - 2022
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2022.5371
Subject(s) - tlr7 , immune system , cancer , acquired immune system , immunology , cancer research , biology , cd8 , dendritic cell , medicine , innate immune system , toll like receptor
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‑γ, TNF‑α 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.