title: Antitumor activity of a novel small molecule TLR7 agonist via immune response induction and tumor microenvironment modulation.
abstract: Immunotherapy is emerging as a powerful and active tumor-specific approach against cancer via triggering the immune system. Toll-like receptors (TLRs) are fundamental elements of the immune system, which facilitate our understanding of the innate and adaptive immune pathways. TLR agonists used as single agents can effectively eradicate tumors due to their potent stimulation of innate and adaptive immunity. We examined the effects of a novel adenine type of TLR7 agonists on both innate and adaptive immune activation in vitro and in vivo. We established the local and distant tumor‑bearing mice derived from murine mammary carcinoma cell line (4T1) to model metastatic disease. Our data demonstrated that SZU101 was able to stimulate innate immune cells to release cytokines at the very high level compared with LPS at the same or lower concentration. Locally intratumoral SZU101 injection can elicit a systemic antitumor effect on murine breast tumor model. SZU101 affected the frequency of intratumoral immune cell infiltration, including the percentage of CD4+ and CD8+ increase, and the ratio of Tregs decrease. Our data reveal that the antitumor effect of SZU101 is associated with multiple mechanisms, inducing tumor‑specific immune response, activation of innate immune cells and modulation of the tumor microenvironment.
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Gao
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Huang
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Boya
authors.initials: B
authors.lastname: Peng
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Siping
authors.initials: S
authors.lastname: Chen
authors.affiliation: Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D013386:Succinates / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; C000604281:SZU-101; D013386:Succinates; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000225:Adenine