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

Zhou,Jianchun; Xu,Yu; Wang,Guansong; Mei,Tonghua; Yang,Hao; Liu,Yuliang

doi:10.3892/ijo.2022.5371

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

Authors:
- Jianchun Zhou
- Yu Xu
- Guansong Wang
- Tonghua Mei
- Hao Yang
- Yuliang Liu
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Affiliations: Respiratory Medicine Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Institute of Respiratory Diseases, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China
Published online on: May 12, 2022 https://doi.org/10.3892/ijo.2022.5371
Article Number: 81
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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