biostudies-literatureSong FShanghai Municipal Health Commission Collaborative Innovation Cluster ProjectShanghai Municipal Health CommissionFudan UniversityPostgraduate Research & Practice Innovation Program of Jiangsu ProvinceNational Natural Science Foundation of ChinaJiangsu Provincial Research HospitalShanghai Science and Technology CommissionEastern Talent Program (Leading project)Shanghai hospital development centerScience Foundation of Zhongshan Hospitale1738https://www.ebi.ac.uk/biostudies/studies/S-EPMC11296886biostudies-literatureUnknown14(8)<h4>Background</h4>The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance.<h4>Objective</h4>This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC.<h4>Methods</h4>Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA Clinical and translational medicineAnlotinib potentiates anti-PD1 immunotherapy via transferrin receptor-dependent CD8⁺ T-cell infiltration in hepatocellular carcinoma.PMC11296886YJXYY202204-YSB072022LJ00522140900600820727158234102722S319018002021ZSCX28201940075211409003002020ZSLC31KYCX23_3423SHDC2023CRD0252019CXJQ02Wang CGSun HXWang PXGuo WSong FHu BWang TLFan JChen ZYang XRCheng JWTang PJLiang XLZhou JfalseAnlotinib potentiates anti-PD1 immunotherapy via transferrin receptor-dependent CD8⁺ T-cell infiltration in hepatocellular carcinoma.<h4>Background</h4>The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance.<h4>Objective</h4>This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC.<h4>Methods</h4>Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA 2024-01-01T00:00:00Z2024 Aug2025-04-18T20:22:31.031Z2025-02-19T02:27:08.412ZS-EPMC112968863909532310.1002/ctm2.1738