The TLR7 agonist induces tumor regression both by promoting CD4+T cells proliferation and by reversing T regulatory cell-mediated suppression via dendritic cells
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Chenchen Wang1,*, Quan Zhou1,*, Xiaofeng Wang1, Xiongyan Wu1, Xuehua Chen1, Jianfang Li1, Zhenggang Zhu1, Bingya Liu1, Liping Su1
1Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
*These authors have contributed equally to this work
Liping Su, e-mail: [email protected]
Bingya Liu, e-mail: [email protected]
Keywords: TLR7, Treg cells, Immune suppression, Anti-tumor effect
Received: October 08, 2014 Accepted: November 16, 2014 Published: December 15, 2014
Treg-induced immunosuppression is now recognized as a key element in enabling tumors to escape immune-mediated destruction. Although topical TLR7 therapies such as imiquimod have been proved successful in the treatment of dermatological malignancy and a number of conditions beyond the FDA-approved indications, the mechanism behind the effect of TLR7 on effector T cell and Treg cell function in cancer immunosurveillance is still not well understood. Here, we found that Loxoribin, one of the TLR7 ligands, could inhibit tumor growth in xenograft models of colon cancer and lung cancer, and these anti-tumor effects of Loxoribin were mediated by promoting CD4+T cell proliferation and reversing Treg-mediated suppression via dendritic cells (DCs). However, deprivation of IL-6 using a neutralizing antibody abrogated the ability of Loxoribin-treated DCs, which reversed the Treg cell-mediated suppression. Furthermore, adoptive transfer of Loxoribin-treated DCs inhibited the tumor growth in vivo. Thus, this study links TLR7 signaling to the functional control of effector T cells and Treg cells and identifies Loxoribin as a new therapeutic strategy in cancer treatment, which may offer new opportunities to improve the outcome of cancer immunotherapy.
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