{"doi":"10.17615/nf2z-7x04","title":"PD-1 and Tim-3 Regulate the Expansion of Tumor Antigen-Specific CD8+ T Cells Induced by Melanoma Vaccines","abstract":"Although melanoma vaccines stimulate tumor antigen (TA)-specific CD8+ T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8+ T cells with regard to the inhibitory T cell co-receptors PD-1 and Tim-3 in metastatic melanoma patients who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant (IFA), CpG oligodeoxynucleotide (CpG) and the HLA-A2-restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid TA-specific CD8+ T-cell responses detected ex vivo, however, TA-specific CD8+ T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8+ T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8+ T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8+ T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T cell responses and increase the likelihood of clinical responses in advanced melanoma patients.","journal":"UNC Libraries","year":2020,"id":117797,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":372524,"name":"Ahmad A. Tarhini","orcid":"0000-0002-3193-9702","position":1,"is_corresponding":false},{"id":549263,"name":"Joe Marc Chauvin","orcid":null,"position":2,"is_corresponding":false},{"id":548505,"name":"Stergios J. Moschos","orcid":"0000-0002-8943-0845","position":3,"is_corresponding":false},{"id":259946,"name":"Ornella Pagliano","orcid":"0000-0001-6745-1744","position":4,"is_corresponding":false},{"id":259947,"name":"Cindy Sander","orcid":"0000-0002-4136-1342","position":5,"is_corresponding":false},{"id":549264,"name":"Bratislav Janjic","orcid":null,"position":6,"is_corresponding":false},{"id":548506,"name":"Zhaojun Sun","orcid":"0000-0002-0931-4044","position":7,"is_corresponding":false},{"id":105025,"name":"Hong Wang","orcid":"0000-0003-0477-2908","position":8,"is_corresponding":false},{"id":108615,"name":"Hassane M. Zarour","orcid":"0000-0003-2525-2688","position":9,"is_corresponding":false},{"id":549265,"name":"Arthur Μ. Krieg","orcid":null,"position":10,"is_corresponding":false},{"id":548507,"name":"Philippe Guillaume","orcid":"0000-0002-6340-0963","position":11,"is_corresponding":false},{"id":549266,"name":"Immanuel F. Luescher","orcid":null,"position":12,"is_corresponding":false},{"id":3016,"name":"Ana. C. Anderson","orcid":"0000-0002-0877-2932","position":13,"is_corresponding":false},{"id":247570,"name":"John M. Kirkwood","orcid":"0000-0002-3570-4476","position":14,"is_corresponding":false},{"id":104281,"name":"Hussein Tawbi","orcid":null,"position":15,"is_corresponding":false},{"id":6940,"name":"Vijay K. Kuchroo","orcid":"0000-0001-7177-2110","position":16,"is_corresponding":false},{"id":549262,"name":"Julien Fourcade","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:54.951170Z","pmid":null,"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":[]}