biostudies-literatureUnknown8(3)Klug JH<h4>Background & aims</h4>Immune checkpoint inhibitor (ICI) therapy has significantly improved the treatment of solid tumors such as hepatocellular carcinoma (HCC); however, most patients fail to respond. Here, we examined whether co-administration of the tumor-penetrating internalizing (i)RGD peptide, which selectively increases tumor vascular permeability in a neuropilin-1-dependent manner, enhances intratumoral delivery and therapeutic efficacy of αPD-L1 in mouse models of HCC.<h4>Methods</h4>αPD-L1, with or without iRGD, was administered intravenously to mice bearing endogenous HCCs (TGFα/c-myc and diethylnitrosamine [DEN]/carbon tetrachloride [CCl₄] models). Tumor growth was monitored by MRI. Immune cell composition and activation were analyzed by flow cytometry. RNA sequenJHEP reports : innovation in hepatology101731https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907498biostudies-literatureCo-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma.PMC12907498Meindl-Beinker NMFinkelmeier FVogl TJZeuzem SDe La Torre CDenk DWaidmann OAliraj BWeigert AKlug JHGermann LBrune BAlcober-Boquet LPiiper AfalseCo-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma.<h4>Background & aims</h4>Immune checkpoint inhibitor (ICI) therapy has significantly improved the treatment of solid tumors such as hepatocellular carcinoma (HCC); however, most patients fail to respond. Here, we examined whether co-administration of the tumor-penetrating internalizing (i)RGD peptide, which selectively increases tumor vascular permeability in a neuropilin-1-dependent manner, enhances intratumoral delivery and therapeutic efficacy of αPD-L1 in mouse models of HCC.<h4>Methods</h4>αPD-L1, with or without iRGD, was administered intravenously to mice bearing endogenous HCCs (TGFα/c-myc and diethylnitrosamine [DEN]/carbon tetrachloride [CCl₄] models). Tumor growth was monitored by MRI. Immune cell composition and activation were analyzed by flow cytometry. RNA sequen2026-01-01T00:00:00Z2026 Mar2026-07-16T05:04:36.35Z2026-07-09T10:37:28.144ZS-EPMC129074984170442210.1016/j.jhepr.2026.101731