{"doi":"10.1084/jem.20231417","title":"Myeloid-targeting immunotherapies overcome inhibitory barriers in immune-evasive neuroblastoma","abstract":"Neuroblastomas are highly heterogeneous tumors originating from neural crest-derived cells destined to form the sympathetic nervous system. Nearly half of high-risk tumors present with amplification of the MYCN proto-oncogene. Here, we describe a Mycn-driven, transplantable, non-germline, genetically engineered mouse model (Mycn-nGEMM). Mycn-nGEMM tumors recapitulate the immune-evasive, macrophage-rich tumor microenvironment of high-risk, MYCN-amplified human neuroblastoma. Treatment of tumor-bearing mice with anti-PD-L1, but not anti-PD-1 or anti-CTLA-4, inhibited tumor growth, profoundly remodeling the tumor microenvironment by depleting anti-inflammatory macrophages and increasing T cell infiltration. Surprisingly, while tumor cells showed low expression of PD-L1, anti-inflammatory macrophages from both murine and human neuroblastoma expressed PD-L1. We identified cytokines, including macrophage migration inhibitory factor, secreted by the Mycn-nGEMM cancer cells that drive expression of PD-L1 on macrophages. Combining anti-PD-L1 with CD40 agonist antibodies further improved survival in Mycn-nGEMM mice, demonstrating the potential for myeloid-targeting immunotherapies to overcome inhibitory barriers in immune-evasive neuroblastoma.","journal":"The Journal of Experimental Medicine","year":2025,"id":532662,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9399,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":969264,"name":"Hiroyuki Yoda","orcid":"0000-0002-5528-8940","position":1,"is_corresponding":false},{"id":634192,"name":"Nicole Nasholm","orcid":"0000-0002-5451-4985","position":2,"is_corresponding":false},{"id":1226851,"name":"Megumi J. Barata","orcid":null,"position":3,"is_corresponding":false},{"id":1413779,"name":"Linyu Wang","orcid":"0009-0008-4952-4426","position":4,"is_corresponding":false},{"id":634186,"name":"Erin F. Simonds","orcid":"0000-0002-3497-4861","position":5,"is_corresponding":false},{"id":634187,"name":"Edbert D Lu","orcid":"0000-0003-1411-6584","position":6,"is_corresponding":false},{"id":798378,"name":"Shannon Wong‐Michalak","orcid":"0000-0002-6932-6039","position":7,"is_corresponding":false},{"id":1413780,"name":"Lauren McHenry","orcid":"0009-0002-2692-049X","position":8,"is_corresponding":false},{"id":1413781,"name":"A. Farrel","orcid":"0000-0003-1942-5992","position":9,"is_corresponding":false},{"id":32686,"name":"Rebecca S. Kaufman","orcid":"0000-0001-8535-9730","position":10,"is_corresponding":false},{"id":1413782,"name":"Vanessa Lopez","orcid":"0000-0002-8340-5411","position":11,"is_corresponding":false},{"id":440334,"name":"Rebekah Kennedy","orcid":"0000-0002-5613-4230","position":12,"is_corresponding":false},{"id":730169,"name":"G. Esteban Fernández","orcid":"0000-0002-8393-9229","position":13,"is_corresponding":false},{"id":381605,"name":"Hiroyuki Shimada","orcid":"0000-0001-5025-7507","position":14,"is_corresponding":false},{"id":810051,"name":"Liron D. Grossmann","orcid":"0000-0002-0692-8921","position":15,"is_corresponding":false},{"id":440340,"name":"Shahab Asgharzadeh","orcid":"0000-0002-0510-3848","position":16,"is_corresponding":false},{"id":240511,"name":"John M. Maris","orcid":"0000-0002-8088-7929","position":17,"is_corresponding":false},{"id":751251,"name":"W. Clay Gustafson","orcid":"0000-0002-1812-5675","position":18,"is_corresponding":false},{"id":351797,"name":"William A. Weiss","orcid":"0000-0003-2230-9132","position":19,"is_corresponding":false},{"id":841675,"name":"Marie Ménard","orcid":"0000-0003-1511-4361","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40658105","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":[]}