{"doi":"10.1016/j.ccell.2023.12.005","title":"Interferon-stimulated neutrophils as a predictor of immunotherapy response","abstract":"Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients—emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Ly6Ehi neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6Ehi neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells. By translating our pre-clinical findings to a cohort of patients with non-small cell lung cancer and melanoma (n = 109), and to public data (n = 1440), we demonstrate the ability of Ly6Ehi neutrophils to predict immunotherapy response in humans with high accuracy (average AUC ≈ 0.9). Overall, our study identifies a functionally active biomarker for use in both mice and humans.","journal":"Cancer Cell","year":2024,"id":416377,"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":153,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":646939,"name":"Tim J. Cooper","orcid":null,"position":1,"is_corresponding":false},{"id":1199607,"name":"Prajakta Kalkar","orcid":"0009-0008-7086-6180","position":2,"is_corresponding":false},{"id":1199608,"name":"Sagie Schif‐Zuck","orcid":"0000-0001-5415-9488","position":3,"is_corresponding":false},{"id":110550,"name":"Ruth Halaban","orcid":"0000-0001-8451-1964","position":4,"is_corresponding":false},{"id":819602,"name":"Antonella Bacchiocchi","orcid":null,"position":5,"is_corresponding":false},{"id":104651,"name":"Iris Kamer","orcid":"0000-0002-1707-4730","position":6,"is_corresponding":false},{"id":1200623,"name":"Abhilash Deo","orcid":null,"position":7,"is_corresponding":false},{"id":1200624,"name":"Bar Manobla","orcid":null,"position":8,"is_corresponding":false},{"id":1200625,"name":"Rotem Menachem","orcid":null,"position":9,"is_corresponding":false},{"id":1200626,"name":"Jozafina Haj-Shomaly","orcid":null,"position":10,"is_corresponding":false},{"id":1200627,"name":"Avital Vorontsova","orcid":null,"position":11,"is_corresponding":false},{"id":1200628,"name":"Ziv Raviv","orcid":null,"position":12,"is_corresponding":false},{"id":1199609,"name":"Chen Buxbaum","orcid":"0000-0003-0400-7405","position":13,"is_corresponding":false},{"id":64654,"name":"Petros Christopoulos","orcid":"0000-0002-7966-8980","position":14,"is_corresponding":false},{"id":104683,"name":"Jair Bar","orcid":"0000-0002-1224-3646","position":15,"is_corresponding":false},{"id":463731,"name":"Michal Lotem","orcid":"0000-0003-1703-8008","position":16,"is_corresponding":false},{"id":68933,"name":"Mario Sznol","orcid":"0000-0002-4359-8749","position":17,"is_corresponding":false},{"id":399212,"name":"Amiram Ariel","orcid":"0000-0002-7469-5728","position":18,"is_corresponding":false},{"id":3339,"name":"Shai S. Shen-Orr","orcid":"0000-0002-6991-7736","position":19,"is_corresponding":false},{"id":491630,"name":"Yuval Shaked","orcid":"0000-0001-9037-3895","position":20,"is_corresponding":false},{"id":1200622,"name":"Madeleine Benguigui","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:56:20.964471Z","pmid":"38181798","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":[]}