{"doi":"10.1101/2024.01.02.573934","title":"STING Licensing of Type I Dendritic Cells Potentiates Antitumor Immunity","abstract":"Abstract Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP (cGAMP) in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations including cancer cells with distinct cellular functions such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here using a polymeric STING-activating nanoparticle (PolySTING) with a “shock-and-lock” dual activation mechanism, we show type 1 conventional dendritic cell (cDC1) is essential for STING-mediated rejection of multiple established and metastatic murine tumors. STING status in the host but not in the cancer cells ( Tmem173 -/- ) is important for antitumor efficacy. Specific depletion of cDC1 ( Batf3 -/- ) or STING deficiency in cDC1 ( XCR1 cre STING fl/fl ) abolished PolySTING efficacy, whereas depletion of other myeloid cells had little effect. Adoptive transfer of wildtype cDC1 in Batf3 -/- mice restored antitumor efficacy while transfer of cDC1 with STING or IRF3 deficiency failed to rescue. PolySTING induced a specific chemokine signature in wildtype but not Batf3 -/- mice. Multiplexed immunohistochemistry analysis of STING-activating cDC1s in resected tumors correlates with patient survival while also showing increased expressions after neoadjuvant pembrolizumab therapy in non-small cell lung cancer patients. Therefore, we have defined that a subset of myeloid cells is essential for STING-mediated antitumor immunity with associated biomarkers for prognosis. One Sentence Summary A “shock-and-lock” nanoparticle agonist induces direct STING signaling in type 1 conventional dendritic cells to drive antitumor immunity with defined biomarkers","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485327,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"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":285062,"name":"Suxin Li","orcid":"0000-0001-6466-6854","position":1,"is_corresponding":false},{"id":1050630,"name":"Maggie Haitian Wang","orcid":"0000-0003-1223-4595","position":2,"is_corresponding":false},{"id":934030,"name":"Xu Wang","orcid":"0000-0001-6920-0375","position":3,"is_corresponding":false},{"id":1201024,"name":"Shuqing Chen","orcid":"0000-0002-0792-3735","position":4,"is_corresponding":false},{"id":285067,"name":"Zhichen Sun","orcid":"0000-0001-7837-8407","position":5,"is_corresponding":false},{"id":362039,"name":"Xiubao Ren","orcid":"0000-0003-4137-2049","position":6,"is_corresponding":false},{"id":285064,"name":"Gang Huang","orcid":"0000-0001-6658-9557","position":7,"is_corresponding":false},{"id":618867,"name":"Baran D. Sumer","orcid":"0000-0002-8371-4388","position":8,"is_corresponding":false},{"id":230829,"name":"Nan Yan","orcid":"0000-0002-0637-3989","position":9,"is_corresponding":false},{"id":230370,"name":"Yang‐Xin Fu","orcid":"0000-0001-8441-6617","position":10,"is_corresponding":false},{"id":285069,"name":"Jinming Gao","orcid":"0000-0003-0726-5098","position":11,"is_corresponding":false},{"id":252142,"name":"Jian Wang","orcid":"0000-0002-9482-5227","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:47.633574Z","pmid":"38260493","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":[]}