{"doi":"10.3389/fimmu.2022.887649","title":"Biodegradable nanoparticles induce cGAS/STING-dependent reprogramming of myeloid cells to promote tumor immunotherapy","abstract":"Cancer treatment utilizing infusion therapies to enhance the patient’s own immune response against the tumor have shown significant functionality in a small subpopulation of patients. Additionally, advances have been made in the utilization of nanotechnology for the treatment of disease. We have previously reported the potent effects of 3-4 daily intravenous infusions of immune modifying poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IMPs; named ONP-302) for the amelioration of acute inflammatory diseases by targeting myeloid cells. The present studies describe a novel use for ONP-302, employing an altered dosing scheme to reprogram myeloid cells resulting in significant enhancement of tumor immunity. ONP-302 infusion decreased tumor growth via the activation of the cGAS/STING pathway within myeloid cells, and subsequently increased NK cell activation via an IL-15-dependent mechanism. Additionally, ONP-302 treatment increased PD-1/PD-L1 expression in the tumor microenvironment, thereby allowing for functionality of anti-PD-1 for treatment in the B16.F10 melanoma tumor model which is normally unresponsive to monotherapy with anti-PD-1. These findings indicate that ONP-302 allows for tumor control via reprogramming myeloid cells via activation of the STING/IL-15/NK cell mechanism, as well as increasing anti-PD-1 response rates.","journal":"Frontiers in Immunology","year":2022,"id":245719,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":449606,"name":"Andrew C. Cogswell","orcid":"0000-0002-6951-6713","position":1,"is_corresponding":false},{"id":582867,"name":"Ming‐Yi Chiang","orcid":null,"position":2,"is_corresponding":false},{"id":881420,"name":"Valerie Eaton","orcid":null,"position":3,"is_corresponding":false},{"id":351375,"name":"Igal Ifergan","orcid":"0000-0003-2945-2580","position":4,"is_corresponding":false},{"id":741876,"name":"Tobias Neef","orcid":"0000-0002-8256-1455","position":5,"is_corresponding":false},{"id":317083,"name":"Dan Xu","orcid":"0000-0002-5315-8552","position":6,"is_corresponding":false},{"id":880861,"name":"Khyati Meghani","orcid":"0000-0002-4113-6284","position":7,"is_corresponding":false},{"id":880862,"name":"Yanni Yu","orcid":"0009-0002-4254-7680","position":8,"is_corresponding":false},{"id":388295,"name":"Sophia M. Orbach","orcid":"0000-0002-1852-6890","position":9,"is_corresponding":false},{"id":875706,"name":"Tushar Murthy","orcid":null,"position":10,"is_corresponding":false},{"id":875707,"name":"Michael T. Boyne","orcid":null,"position":11,"is_corresponding":false},{"id":625496,"name":"Adam Elhofy","orcid":"0000-0002-3060-7829","position":12,"is_corresponding":false},{"id":260792,"name":"Lonnie D. Shea","orcid":"0000-0002-9296-9673","position":13,"is_corresponding":false},{"id":242016,"name":"Joshua J. Meeks","orcid":"0000-0002-5444-5510","position":14,"is_corresponding":false},{"id":242015,"name":"Stephen D. Miller","orcid":"0000-0002-9556-0718","position":15,"is_corresponding":false},{"id":260784,"name":"Joseph R. Podojil","orcid":"0000-0002-5818-8515","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:39.284121Z","pmid":"36059473","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":[]}