{"doi":"10.3389/fcell.2020.00210","title":"Intra-Tumoral Delivery of IL-27 Using Adeno-Associated Virus Stimulates Anti-tumor Immunity and Enhances the Efficacy of Immunotherapy","abstract":"IL-27 is an anti-inflammatory cytokine that has been shown to have potent anti-tumor activity. We recently reported that systemic delivery of IL-27 using recombinant adeno-associated virus (rAAV) induced depletion of Tregs and significantly enhanced the efficacy of cancer immunotherapy in a variety of mouse tumor models. A potential caveat of systemic delivery of IL-27 using rAAV is that there is no practical method to terminate IL-27 production when its biological activity is no longer needed. Therefore, in this work, we tested if directly injecting AAV-IL-27 into tumors could lead to similar anti-tumor effect yet avoiding uncontrolled IL-27 production. We found that high levels of IL-27 was produced in tumors and released to peripheral blood after AAV-IL-27 intra-tumoral injection. AAV-IL-27 local therapy showed potent anti-tumor activity in mice bearing plasmacytoma J558 tumors and modest anti-tumor activity in mice bearing B16.F10 tumors. Intra-tumoral injection of AAV-IL-27 induced infiltration of immune effectors including CD8+ T cells and NK cells into tumors, caused systemic reduction of Tregs and stimulated protective immunity. Mechanistically, we found that IL-27 induced T cell expression of CXCR3 in an IL-27R-dependent manner. Additionally, we found that AAV-IL-27 local therapy had significant synergy with anti-PD-1 or T cell adoptive transfer therapy. Importantly, in mice whose tumors were completely rejected, IL-27 serum levels were significantly reduced or diminished. Thus, intra-tumoral injection of AAV-IL-27 is a feasible approach that can be used alone and in combination with anti-PD-1 antibody or T cell adoptive transfer for the treatment of cancer.","journal":"Frontiers in Cell and Developmental Biology","year":2020,"id":100592,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9444,"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":493713,"name":"Miao Ding","orcid":"0000-0001-8674-2731","position":1,"is_corresponding":false},{"id":493714,"name":"Jianmin Zhu","orcid":"0009-0005-9878-7239","position":2,"is_corresponding":false},{"id":108380,"name":"Jin-Qing Liu","orcid":"0009-0001-6761-5400","position":3,"is_corresponding":false},{"id":269761,"name":"Xueliang Pan","orcid":"0000-0002-2342-3212","position":4,"is_corresponding":false},{"id":382614,"name":"Kalpana Ghoshal","orcid":"0000-0002-8663-7787","position":5,"is_corresponding":false},{"id":493715,"name":"Xue‐Feng Bai","orcid":"0000-0001-9476-8376","position":6,"is_corresponding":false},{"id":493712,"name":"Aiyan Hu","orcid":"0000-0002-2561-3271","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T22:39:01.863288Z","pmid":"32292786","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":[]}