{"doi":"10.1016/j.celrep.2024.114141","title":"Batf3+ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy","abstract":"The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8 + T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3 + DCs and CD8 + T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3 + DCs within the TME is associated with CD8 + T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3 + DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4-1BB/4-1BB ligand (4-1BBL) axis during this process.","journal":"Cell Reports","year":2024,"id":423723,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"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":355291,"name":"Brendan Horton","orcid":"0000-0002-9551-9002","position":1,"is_corresponding":false},{"id":553608,"name":"Emily F. Higgs","orcid":"0000-0003-2477-8549","position":2,"is_corresponding":false},{"id":625373,"name":"Ken Hatogai","orcid":"0000-0001-7888-7965","position":3,"is_corresponding":false},{"id":1199504,"name":"Anna Martinez","orcid":"0000-0001-7245-9687","position":4,"is_corresponding":false},{"id":320256,"name":"Jason W. Shapiro","orcid":"0000-0002-1321-8418","position":5,"is_corresponding":false},{"id":1220106,"name":"Danny EC Kim","orcid":null,"position":6,"is_corresponding":false},{"id":92110,"name":"Yuanyuan Zha","orcid":"0000-0002-0574-7352","position":7,"is_corresponding":false},{"id":311890,"name":"Randy F. Sweis","orcid":"0000-0002-0497-9637","position":8,"is_corresponding":false},{"id":92113,"name":"Thomas F. Gajewski","orcid":"0000-0001-5727-3972","position":9,"is_corresponding":false},{"id":1219494,"name":"Andrea Ziblat","orcid":"0000-0003-1469-8836","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T01:58:01.889748Z","pmid":"38656869","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":[]}