{"doi":"10.1016/j.celrep.2024.114875","title":"Comparing neoantigen cancer vaccines and immune checkpoint therapy unveils an effective vaccine and anti-TREM2 macrophage-targeting dual therapy","abstract":"The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1 + TCF-1 + neoAg-specific CD8 T cells in tumors. Anti-CTLA-4 and/or anti-PD-1 ICT promotes intratumoral TCF-1 − neoAg-specific CD8 T cells, although their phenotype depends in part on the specific ICT used. Anti-CTLA-4 also prompts substantial changes to CD4 T cells, including induction of ICOS + Bhlhe40 + T helper 1 (Th1)-like cells. Although neoAg vaccines or ICTs expand iNOS + macrophages, neoAg vaccines maintain CX3CR1 + CD206 + macrophages expressing the TREM2 receptor, unlike ICT, which suppresses them. TREM2 blockade enhances neoAg vaccine efficacy and is associated with fewer CX3CR1 + CD206 + macrophages and induction of neoAg-specific CD8 T cells. Our findings highlight different mechanisms underlying neoAg vaccines and different forms of ICT and identify combinatorial therapies to enhance neoAg vaccine efficacy.","journal":"Cell Reports","year":2024,"id":433372,"datarank":0.5387235104124763,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.13251598024714484,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.13251598024714484,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":11,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE276902","GSE276904"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":837085,"name":"Alexander S. Shavkunov","orcid":"0000-0003-2390-9391","position":1,"is_corresponding":false},{"id":582339,"name":"Qi Miao","orcid":"0000-0003-2782-1581","position":2,"is_corresponding":false},{"id":1170831,"name":"Akata Saha","orcid":"0000-0002-3125-2871","position":3,"is_corresponding":false},{"id":1238652,"name":"Tomoyuki Minowa","orcid":"0000-0002-8353-036X","position":4,"is_corresponding":false},{"id":109966,"name":"Martina Molgora","orcid":"0000-0001-7328-2844","position":5,"is_corresponding":false},{"id":865887,"name":"Charmelle D. Williams","orcid":"0000-0001-8342-587X","position":6,"is_corresponding":false},{"id":638107,"name":"Mehdi Chaib","orcid":"0000-0002-4793-0120","position":7,"is_corresponding":false},{"id":866690,"name":"Anna M. Highsmith","orcid":null,"position":8,"is_corresponding":false},{"id":858612,"name":"Josué E. Pineda","orcid":"0000-0002-8132-1804","position":9,"is_corresponding":false},{"id":1205026,"name":"Sayan Alekseev","orcid":null,"position":10,"is_corresponding":false},{"id":630232,"name":"Elise Alspach","orcid":"0000-0002-2740-9768","position":11,"is_corresponding":false},{"id":553724,"name":"Kenneth H. Hu","orcid":"0000-0002-0294-0202","position":12,"is_corresponding":false},{"id":71132,"name":"Marco Colonna","orcid":"0000-0001-5222-4987","position":13,"is_corresponding":false},{"id":267958,"name":"Kristen E. Pauken","orcid":"0000-0002-0974-2751","position":14,"is_corresponding":false},{"id":108501,"name":"Ken Chen","orcid":"0000-0003-4013-5279","position":15,"is_corresponding":false},{"id":809136,"name":"Matthew M. Gubin","orcid":"0000-0001-7443-2752","position":16,"is_corresponding":false},{"id":865886,"name":"Sunita Keshari","orcid":"0000-0003-4889-8430","position":0,"is_corresponding":true}],"reference_count":120,"raw_metadata":null,"created_at":"2026-07-19T01:59:44.444627Z","pmid":"39446585","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":[]}