{"doi":"10.1172/jci163291","title":"Combination of AFP vaccine and immune checkpoint inhibitors slows hepatocellular carcinoma progression in preclinical models","abstract":"Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.","journal":"Journal of Clinical Investigation","year":2023,"id":322420,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":833796,"name":"Shanshan Deng","orcid":"0000-0002-2166-5082","position":1,"is_corresponding":false},{"id":51646,"name":"Jiejie Xu","orcid":"0000-0001-7431-9063","position":2,"is_corresponding":false},{"id":666421,"name":"Benjamin L. Green","orcid":"0000-0002-5772-198X","position":3,"is_corresponding":false},{"id":1035960,"name":"Honghua Zhang","orcid":"0000-0001-6517-7649","position":4,"is_corresponding":false},{"id":865109,"name":"Guofei Cui","orcid":"0009-0005-5624-0403","position":5,"is_corresponding":false},{"id":1035961,"name":"Yi Zhou","orcid":"0009-0007-9646-6057","position":6,"is_corresponding":false},{"id":103949,"name":"Yi Zhang","orcid":"0000-0001-9861-4681","position":7,"is_corresponding":false},{"id":1035962,"name":"Hongwei Xu","orcid":"0000-0002-0470-705X","position":8,"is_corresponding":false},{"id":1036578,"name":"Fapeng Zhang","orcid":null,"position":9,"is_corresponding":false},{"id":828478,"name":"Rui Mao","orcid":"0000-0002-6737-2939","position":10,"is_corresponding":false},{"id":594767,"name":"Sheng Zhong","orcid":"0000-0001-6908-3519","position":11,"is_corresponding":false},{"id":1035963,"name":"Thorsten Cramer","orcid":"0000-0002-6462-239X","position":12,"is_corresponding":false},{"id":278057,"name":"Matthias Evert","orcid":"0009-0001-8412-9682","position":13,"is_corresponding":false},{"id":270014,"name":"Diego F. Calvisi","orcid":"0000-0002-6038-8567","position":14,"is_corresponding":false},{"id":499472,"name":"Yukai He","orcid":"0000-0001-7636-5549","position":15,"is_corresponding":false},{"id":432879,"name":"Chao Liu","orcid":"0000-0003-0316-4994","position":16,"is_corresponding":false},{"id":1360,"name":"Xin Chen","orcid":"0000-0002-9588-0164","position":17,"is_corresponding":false},{"id":270012,"name":"Xinjun Lu","orcid":"0000-0002-7643-0854","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:07:42.497873Z","pmid":"37040183","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}