Fig. 8

TMSB10 could be a potential immunotherapy target for glioma patients, and knockdown of TMSB10 improves the efficacy of selumetinib and anti-PD1 in glioma. A Spearman’s correlation analysis between TMSB10 and the bioavailability (AUC) of the drugs that have undergone clinical trials or received FDA approval was collected from the CellMiner database (https://discover.nci.nih.gov/cellminer/). B Comparison of the estimated selumetinib AUC between the TMSB10-high group and the TMSB10 low group. C Animal experiment protocol design process. D Bioluminescent image showing the tumor size of mice coimplanted with THP-1 cells and luciferase-labeled GSC267 expressing sh-TMSB10 or sh-NC and treated with selumetinib (50 mg/ml) for the indicated times. The quantification histogram represents the bioluminescent flux. Data represent the mean ± SD; n = 5 for each group. E Kaplan–Meier survival curves showing the mice coimplanted with THP-1 cells and luciferase-labeled GSCs expressing sh-TMSB10 or sh-NC and treated with selumetinib (50 mg/ml). Log-rank analysis was used; n = 5 for each group. F Expression of TMSB10 in distinct anti-PD1 clinical response groups. G The proportion of patients who responded to anti-PD1 immunotherapy in the low or high TMSB10 expression groups. R, response; NR, no response. H ROC curve quantifying the predictive value of TMSB10 in GBM patients treated with anti-PD1 therapy (AUC, 0.757). Kaplan–Meier curves for (I) the OS of GBM patients (log-rank test P = 0.027) and J survival duration after anti-PD1 treatment (log-rank test P < 0.001 in the PD1 dataset. K GBOs at 1 week were cocultured with CM from GSC 267 cells, transfected with sh-TMSB10 or sh-NC, and treated with PD1 antibody (5 µM) and/or selumetinib (7.5 µM) for 5 days as indicated. IF staining for KI67 and CD44 in GBO sections showed that knockdown of TMSB10 enhanced the effect of anti-PD1 and selumetinib therapy; scale bars: 10 μm. Histogram representing statistical data for proportion of positive area; n = 3 for each group. All data are presented as the mean ± SD. The statistical significance is shown as follows: ns > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001