ArticleHepatology (Baltimore, Md.)2022
Enhancing the therapeutic efficacy of programmed death ligand 1 antibody for metastasized liver cancer by overcoming hepatic immunotolerance in mice.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 28 citations in OpenAlex.
- Efficacious suppression of primary and metastasized liver tumors by polyIC-loaded lipid nanoparticles.Hepatology (Baltimore, Md.) · 2026Article
- Advancing liver cancer immunotherapy beyond checkpoint blockade.Science China. Life sciences · 2026Article
- Unexpected Therapeutic Implications: The Abscopal Effect in the Management of Hepatocellular Carcinoma.Cancers · 2026Review
- GPC3-based circular RNA vaccine suppresses hepatocellular carcinoma progression by activating adaptive immune responses.Hepatology (Baltimore, Md.) · 2025Article
- PolyIC as an adjuvant outperforms anti-VEGF in combination with anti-PD-L1 therapy in mouse liver tumor models.Hepatology communications · 2025Article
- Novel immune drug combination induces tumour microenvironment remodelling and reduces the dosage of anti-PD-1 antibody.Scientific reports · 2025Article
- Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.eGastroenterology · 2025Review
- Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation.Cancer immunology, immunotherapy : CII · 2024Article
- Effects of the subtypes of apolipoprotein E on immune inhibition and prognosis in patients with Hepatocellular Carcinoma.Journal of cancer research and clinical oncology · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling.Journal of pharmaceutical analysis · 2024Article
- Combination of AFP vaccine and immune checkpoint inhibitors slows hepatocellular carcinoma progression in preclinical models.The Journal of clinical investigation · 2023Article
- Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities.Molecular therapy oncolytics · 2023Review
- Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.Bone research · 2023Review
- Patient-derived xenograft model in colorectal cancer basic and translational research.Animal models and experimental medicine · 2023Review
- Hepatocellular Carcinoma Subtyping and Prognostic Model Construction Based on Chemokine-Related Genes.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2023Article
- Research Progress on the Microenvironment and Immunotherapy of Advanced Non-Small Cell Lung Cancer With Liver Metastases.Frontiers in oncology · 2022Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsImmunotherapy with programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade has shown low response rates in liver cancer patients, with the underlying mechanisms unclear. To decipher a specific impact of the liver microenvironment, we compared the effects of anti-PD-L1 antibody (αPD-L1) blockade on the same tumor grown s.c. or in the liver. APPROACH AND
resultsWe generated s.c. tumors in mice by inoculating MC38 colorectal cancer (CRC) cells under the skin and metastatic liver tumors by portal vein or splenic injection of CRC cells. Tumor-bearing mice were treated by i.p. injection of αPD-L1, polyinosinic:polycytidylic acid (poly[I:C]), or both. αPD-L1 monotherapy significantly suppressed s.c. tumor growth, but showed no effect on metastatic liver tumors. However, the combination of αPD-L1 with poly(I:C), an innate immunity-stimulating reagent, robustly inhibited tumor progression in liver. The combination therapy effectively down-regulated myeloid-derived suppressor cells (MDSCs), but up-regulated ratios of M1/M2 macrophages, CD8/CD4, and CD8/regulatory T (Treg) cells infiltrated into liver tumors and whole liver. A group of long-lasting T-bet
conclusionsThe poor response of liver cancers to αPD-L1 therapy is largely attributable to a unique hepatic immunotolerant microenvironment, independent of tumor origins or types. The success of a combinatorial immunotherapy relies on coordinated inhibition or activation of various innate and adaptive immune cell activities.
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