{"doi":"10.3389/fimmu.2020.02090","title":"Tumor-Derived cGAMP Regulates Activation of the Vasculature","abstract":"Intratumoral recruitment of immune cells following innate immune activation is critical for anti-tumor immunity and involves cytosolic dsDNA sensing by the cGAS/STING pathway. We have previously shown that KRAS-LKB1 (KL) mutant lung cancer, which is resistant to PD-1 blockade, exhibits silencing of STING, impaired tumor cell production of immune chemoattractants, and T cell exclusion. Since the vasculature is also a critical gatekeeper of immune cell infiltration into tumors, we developed a novel microfluidic model to study KL tumor-vascular interactions. Notably, dsDNA priming of LKB1-reconstituted tumor cells activates the microvasculature, even when tumor cell STING is deleted. cGAS-driven extracellular export of 2'3' cGAMP by cancer cells activates STING signaling in endothelial cells and cooperates with type 1 interferon to increase vascular permeability and expression of E selectin, VCAM-1, and ICAM-1 and T cell adhesion to the endothelium. Thus, tumor cell cGAS-STING signaling not only produces T cell chemoattractants, but also primes tumor vasculature for immune cell escape.","journal":"Frontiers in Immunology","year":2020,"id":60622,"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":61,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"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":320274,"name":"Shriram K. Sundararaman","orcid":"0000-0002-6686-6945","position":1,"is_corresponding":false},{"id":288153,"name":"Sarah E. Shelton","orcid":"0000-0002-9358-058X","position":2,"is_corresponding":false},{"id":227593,"name":"Erik H. Knelson","orcid":"0000-0003-4087-2017","position":3,"is_corresponding":false},{"id":38303,"name":"Navin R. Mahadevan","orcid":"0000-0002-6805-8861","position":4,"is_corresponding":false},{"id":320275,"name":"Ryohei Yoshida","orcid":"0000-0002-2959-9972","position":5,"is_corresponding":false},{"id":303825,"name":"Tetsuo Tani","orcid":"0000-0001-5719-2697","position":6,"is_corresponding":false},{"id":269864,"name":"Elena V. Ivanova","orcid":"0000-0002-5069-4974","position":7,"is_corresponding":false},{"id":320276,"name":"Israel Cañadas","orcid":"0000-0001-6474-711X","position":8,"is_corresponding":false},{"id":292898,"name":"Tatsuya Osaki","orcid":"0000-0001-7174-0629","position":9,"is_corresponding":false},{"id":320277,"name":"Sharon Wei Ling Lee","orcid":"0000-0003-4965-0234","position":10,"is_corresponding":false},{"id":227609,"name":"Tran C. Thai","orcid":"0000-0003-4799-0876","position":11,"is_corresponding":false},{"id":320278,"name":"Saemi Han","orcid":"0000-0001-8933-1567","position":12,"is_corresponding":false},{"id":320279,"name":"Brandon Piel","orcid":"0000-0003-4805-3358","position":13,"is_corresponding":false},{"id":321892,"name":"Sean Gilhooley","orcid":null,"position":14,"is_corresponding":false},{"id":227616,"name":"Cloud P. Paweletz","orcid":"0000-0002-2287-5663","position":15,"is_corresponding":false},{"id":320280,"name":"Valeria Chiono","orcid":"0000-0003-2067-7732","position":16,"is_corresponding":false},{"id":266248,"name":"Roger D. Kamm","orcid":"0000-0002-7232-304X","position":17,"is_corresponding":false},{"id":303824,"name":"Shunsuke Kitajima","orcid":"0000-0001-6532-2543","position":18,"is_corresponding":false},{"id":227617,"name":"David A. Barbie","orcid":"0000-0002-5422-4275","position":19,"is_corresponding":false},{"id":320273,"name":"Marco Campisi","orcid":"0000-0002-9288-5285","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T21:09:05.493770Z","pmid":"33013881","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":[]}