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. 2021 May 14;29(10):2995–3010. doi: 10.1016/j.ymthe.2021.05.012

Figure 2.

Figure 2

Simvastatin represses tumor expression of PD-L1 and enhances cytotoxic T lymphocyte (CTL) infiltration in CRC patients

(A) PD-L1 mRNA expression in HCT116 and RKO cells treated with simvastatin or negative control. (B) PD-L1 protein expression in HCT116 and RKO cells treated with simvastatin or negative control. (C) PD-L1 protein expression in xenograft tumors from HCT116 and RKO cells. (D) PD-L1 protein expression in xenograft tumors from RKO cells. (E) Graphic illustration of a human PDX model-based therapeutic study. PDX tumors were generated from CRC patients and treated with simvastatin or negative control. (F) In vivo analyses of tumor (left panel) and growth (right panel) in mice that were subcutaneously implanted with tumor tissues from CRC patients and treated with simvastatin or negative control (50 mg/kg) five times weekly for 3 weeks (n = 6). Results are presented as mean ± SD. ∗∗∗p < 0.001. (G) PD-L1 protein expression in the PDX model treated with simvastatin or negative control. (H) Representative immunohistochemical images were shown in randomly selected tumor. (I) Graphic illustration of C57BL/6 mice injected with 2 × 106 MC38 tumor cells. At day 7 after tumor inoculation, simvastatin or negative control was intragastric administrated into tumor-bearing mice (50 mg/kg, five times weekly for 3 weeks). Anti-PD-L1 antibody was intraperitoneally injected combined with simvastatin in addition (10 μg/g, two times weekly for 3 weeks). (J) In vivo analyses of tumors (upper panel) and their growth (bottom panel) in C57BL/6 mice that were subcutaneously injected with 2 × 106 MC38 tumor cells and treated with simvastatin or combined with anti-PD-L1 antibody (n = 6). Results are presented as mean ± SD. ∗∗∗p < 0.001. (K) PD-L1 protein expression in the C57BL/6 mice model treated with simvastatin or negative control. (L) CD8+ T cells in PBMC and TILs were analyzed by flow cytometry. Experiments were performed with at least three biological replicates and are representative of at least two independent experiments. The results are presented as mean ± SD. ∗∗p < 0.01, ∗∗∗p < 0.001.