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. 2023 Apr 5;72(9):1758–1773. doi: 10.1136/gutjnl-2022-328364

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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PPARγ antagonist T0070907 averts ICB resistance in orthotopic HCC models. (A) Combinatory treatment schedule of T0070907 and anti-PD-L1 antibody 10F.9G2 in mice bearing Hepa1-6 or RIL-175-PD-L1R tumours. (B) Representative liver tumour photos and tumour weights of indicated groups in Hepa1-6 and (C) RIL-175-derived ICB-resistant models (n=8 to 10). (D) ELISA analysis of VEGF-A secretion levels of indicated groups in Hepa1-6 and (E) RIL-175-derived ICB-resistant models (n=7 to 8). (F) The ratios of CD8⁺ T/PMN-MDSC in Hepa1-6 and (G) RIL-175 resistant tumours from indicated groups (n=8). (H) The ratios of cytotoxic/exhausted CD8⁺ T cell in Hepa1-6 and (I) RIL-175 resistant tumours from indicated groups (n=8). (J) Kaplan-Meier survival analysis of mice from indicated groups in Hepa1-6 and (K) RIL-175-derived ICB-resistant models (n=9 to 14). Data represent as mean±SD. Statistical significance was assessed by unpaired two-tailed Student’s t-test for (B)–(I), and by two-sided log-rank (Mantel-Cox) test for (J) and (K). *P<0.05; **p<0.01; ***p<0.001; ****p<0.0001. IFN, interferon; MDSC, myeloid-derived suppressor cell; MFI, mean fluorescence intensity; PD-L1R, programmed death-1-ligand-1 resistant; PMN, polymorphonuclear; PPARγ, peroxisome proliferator-activated receptor-gamma; TIM, T cell immunoglobulin; TME, tumour microenvironment; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor.