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Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: RORγt agonist enhances anti-PD-1 therapy by promoting monocyte-derived dendritic cells through CXCL10 in cancers

Fig. 1

Identification of the selective RORγt agonist 8-074. a High expression of RORC correlated with a better prognosis in lung adenocarcinoma (LUAD) patients. Kaplan–Meier survival curves for patients with LUAG from TCGA. b The mRNA level of PDCD1 was negatively correlated with RORC expression in LUAD in TCGA. c Expression of CD8A in the IL17A high expression and IL17A low expression groups in LUAD samples from TCGA (***P < 0.001). d and e Chemical structure of LYC-55716 or 8-074. f Key resides in RORγt protein (PDB ID: 6W9I; Resolution: 1.61 Å) binding to LYC-55716 (yellow stick) and 8-074 (green stick). The hydrogen bond interaction is shown as a red dotted line. Left: Biacore analysis of RORγt protein binding to LYC-55716. Right: Biacore analysis of RORγt protein binding to 8-074. g Biacore binding affinity determination. Sensorgram and saturation curve of the titration of 8-074 on the RORγt LBD protein or the RORγt LBD mutated protein. h The activity of 8-074 in Gal4 reporter gene assays of the three ROR subtypes. 8-074 showed RORγt agonist activity in the Gal4 reporter assay with an EC50 of 119 nM. i The dose–response curve was obtained by fitting a sigmoidal curve to data obtained from stimulation of mouse Tc17 cells using 8-074 concentrations ranging from 0.001 to 320 nM, Th17% was determined using flow cytometry. An EC50 value of 11.21 nM was obtained. j 8-074 (mg/kg) was injected into C57/BL6 mice via i.v. or i.g. The changes in the drug blood concentration in vivo were detected at different time points (n = 3). All error bars represent mean ± SD. Experiments were repeated three times with consistent results

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