{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:52:13Z","timestamp":1791874333550,"version":"4.3.4"},"reference-count":81,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82003879"],"award-info":[{"award-number":["82003879"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82003879"],"award-info":[{"award-number":["82003879"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Science and Technology Department of Sichuan Province","award":["2023NSFSC1928"],"award-info":[{"award-number":["2023NSFSC1928"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2023NSFSC1928"],"award-info":[{"award-number":["2023NSFSC1928"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Science and Technology Department of Sichuan Province","award":["2023NSFSC1992"],"award-info":[{"award-number":["2023NSFSC1992"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2023NSFSC1992"],"award-info":[{"award-number":["2023NSFSC1992"]}],"id":[{"id":"https:\/\/ror.org\/04323m874","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Project of State Administration of Traditional Chinese Medicine of China","award":["ZYYCXTD-D-202209"],"award-info":[{"award-number":["ZYYCXTD-D-202209"]}]},{"name":"Project of Sichuan Provincial Administration of Traditional Chinese Medicine","award":["2022C001"],"award-info":[{"award-number":["2022C001"]}],"id":[{"id":"https:\/\/ror.org\/03x55t826","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Project of Sichuan Provincial Administration of Traditional Chinese Medicine","award":["2024ZD02"],"award-info":[{"award-number":["2024ZD02"]}],"id":[{"id":"https:\/\/ror.org\/03x55t826","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources","award":["SKLTCM202205"],"award-info":[{"award-number":["SKLTCM202205"]}]},{"name":"Sichuan University Interdisciplinary Innovation Fund","id":[{"id":"https:\/\/ror.org\/011ashp19","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fundamental Research Funds for the Central Universities"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The JAK-STAT pathway (JSP) is a well-known oncogenic cascade; however, recent clinical trials have detected JSP upregulation in breast cancer following anti-PD-1 immunotherapy. This paradoxical observation warrants further investigation into JSP\u2019s intercellular heterogeneity, tumor dynamics, molecular mechanisms, and clinical implications for immunotherapy. JSP expression showed dynamic shifts during breast cancer progression, with higher levels in T cells and paracancerous epithelial cells. In human breast cancer tumor cells, elevated JSP is highly correlated with malignant phenotypes. JSP-high tumor cells overexpressed oncogenic pathways, while exhibiting increased immunosuppressive signaling via the MIF-CD74 signaling axis. In T cells, higher JSP levels were associated with enhanced cytotoxic activity, improved differentiation, and reduced exhaustion, reflecting robust anti-tumor immunity. Analysis of immunotherapy datasets revealed that higher JSP levels were associated with improved responses toward PD-1 inhibitors, particularly in triple-negative breast cancer (TNBC) patients, with JSP serving as a predictive biomarker for immunotherapy sensitivity. As a key JSP component, STAT4 exerts dual roles in breast cancer: it drives tumorigenesis in malignant cells, sustains breast epithelial cell proliferation, and bolsters T-cell anti-tumor functionality, while also acting as a highly accurate biomarker for predicting immunotherapy response. This indicates that JSP targeting demands a nuanced approach: broad inhibition may impair anti-tumor immunity, and optimized therapeutic strategies paired with precise biomarkers are critical to maximize JSP\u2019s utility in breast cancer immunotherapy. Our findings highlight JSP\u2019s functional heterogeneity in epithelial, tumor, and T cells, with high JSP activity correlating with enhanced immunotherapy efficacy in breast cancer.<\/jats:p>","DOI":"10.7554\/elife.110635","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T15:30:27Z","timestamp":1775575827000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.110635","source":"Crossref","is-referenced-by-count":1,"title":["JAK-STAT pathway heterogeneity governs immunotherapy response in breast cancer"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-5145","authenticated-orcid":true,"given":"Jianbo","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/007mrxy13","id-type":"ROR","asserted-by":"publisher"}],"name":"West China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Heng","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/007mrxy13","id-type":"ROR","asserted-by":"publisher"}],"name":"West China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Hailin","family":"Tang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0400g8r85","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047d8yx24","id-type":"ROR","asserted-by":"publisher"}],"name":"Chongqing Hospital of Traditional Chinese Medicine","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-4426","authenticated-orcid":true,"given":"Fu","family":"Peng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/007mrxy13","id-type":"ROR","asserted-by":"publisher"}],"name":"West China School of Pharmacy, Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.tips.2025.10.015","type":"journal-article","article-title":"Sodium\u2019s role and therapeutic targeting in cancer","volume":"47","author":"An","year":"2026","journal-title":"Trends in Pharmacological Sciences"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03095","type":"journal-article","article-title":"Immune suppression mediated by STAT4 deficiency promotes lymphatic metastasis in HNSCC","volume":"10","author":"Anderson","year":"2019","journal-title":"Frontiers in Immunology"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02476-1","type":"journal-article","article-title":"Heterogeneity of triple negative breast cancer: current advances in subtyping and treatment implications","volume":"41","author":"Asleh","year":"2022","journal-title":"Journal of Experimental & Clinical Cancer Research"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/s41591-021-01323-8","type":"journal-article","article-title":"A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer","volume":"27","author":"Bassez","year":"2021","journal-title":"Nature Medicine"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1158\/0008-5472.CAN-22-2682","type":"journal-article","article-title":"Spatial transcriptomic analysis of a diverse patient cohort reveals a conserved architecture in triple-negative breast cancer","volume":"83","author":"Bassiouni","year":"2023","journal-title":"Cancer Research"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.molcel.2019.09.030","type":"journal-article","article-title":"Mechanisms controlling PD-L1 expression in cancer","volume":"76","author":"Cha","year":"2019","journal-title":"Molecular Cell"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-022-01236-2","type":"journal-article","article-title":"R code and downstream analysis objects for the scRNA-seq atlas of normal and tumorigenic human breast tissue","volume":"9","author":"Chen","year":"2022","journal-title":"Scientific Data"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111717","type":"journal-article","article-title":"Preclinical development and clinical studies of targeted JAK\/STAT combined Anti-PD-1\/PD-L1 therapy","volume":"130","author":"Chen","year":"2024","journal-title":"International Immunopharmacology"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62132-y","type":"journal-article","article-title":"Metabolism archetype cancer cells induce protumor TREM2+ macrophages via oxLDL-mediated metabolic interplay in hepatocellular carcinoma","volume":"16","author":"Chu","year":"2025","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.mce.2017.01.035","type":"journal-article","article-title":"JAK\/STAT disruption induces immuno-deficiency: rationale for the development of JAK inhibitors as immunosuppressive drugs","volume":"451","author":"Cornez","year":"2017","journal-title":"Molecular and Cellular Endocrinology"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2024.100263","type":"journal-article","article-title":"IL-12 family cytokines and autoimmune diseases: a potential therapeutic target?","volume":"10","author":"Cui","year":"2025","journal-title":"Journal of Translational Autoimmunity"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-023-00508-3","type":"journal-article","article-title":"Immunotherapy in breast cancer: an overview of current strategies and perspectives","volume":"9","author":"Debien","year":"2023","journal-title":"NPJ Breast Cancer"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.681476","type":"journal-article","article-title":"Current triple-negative breast cancer subtypes: dissecting the most aggressive form of breast cancer","volume":"11","author":"Ensenyat-Mendez","year":"2021","journal-title":"Frontiers in Oncology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/S1470-2045(23)00579-X","type":"journal-article","article-title":"Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial","volume":"25","author":"Fan","year":"2024","journal-title":"The Lancet. Oncology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1038\/s41588-025-02289-w","type":"journal-article","article-title":"ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L","volume":"57","author":"Feng","year":"2025","journal-title":"Nature Genetics"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adj7808","type":"journal-article","article-title":"Interferon-induced senescent CD8+ T cells reduce anti-PD1 immunotherapy efficacy in early triple-negative breast cancer","volume":"17","author":"Fu","year":"2025","journal-title":"Science Translational Medicine"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1016\/S0140-6736(16)31891-8","type":"journal-article","article-title":"Breast cancer","volume":"389","author":"Harbeck","year":"2017","journal-title":"The Lancet"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1182\/blood-2013-03-484642","type":"journal-article","article-title":"The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo","volume":"122","author":"Heine","year":"2013","journal-title":"Blood"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-SITC2023.1212","type":"journal-article","article-title":"Bioengineered tumour-targeted interleukin-12 selectively cures murine triple-negative breast cancer (TNBC)","volume":"11","author":"Herpels","year":"2023","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25393-x","type":"journal-article","article-title":"Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape","volume":"12","author":"Hicks","year":"2021","journal-title":"Nature Communications"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00791-1","type":"journal-article","article-title":"The JAK\/STAT signaling pathway: from bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.64898\/2026.01.31.701004","type":"preprint","article-title":"Single-cell profiling of synchronous multi-organ metastasis reveals a systemic CD74+ lipid-associated macrophage niche driving polymetastatic breast cancer","volume-title":"bioRxiv","author":"Insua-Rodr\u00edguez","year":"2026"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.ccell.2019.02.001","type":"journal-article","article-title":"Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies","volume":"35","author":"Jiang","year":"2019","journal-title":"Cancer Cell"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"265","DOI":"10.2147\/BCTT.S516542","type":"journal-article","article-title":"Diagnosis, prognosis, and treatment of triple-negative breast cancer: a review","volume":"17","author":"Jie","year":"2025","journal-title":"Breast Cancer"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02176-8","type":"journal-article","article-title":"PD-1\/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies","volume":"23","author":"Jin","year":"2024","journal-title":"Molecular Cancer"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2024.110447","type":"journal-article","article-title":"Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024)","volume":"36","author":"Kang","year":"2025","journal-title":"Chinese Chemical Letters"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","type":"journal-article","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nature Medicine"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.107095","type":"journal-article","article-title":"Targeting JAK2\/STAT3 for the treatment of cancer: a review on recent advancements in molecular development using structural analysis and SAR investigations","volume":"143","author":"Kohal","year":"2024","journal-title":"Bioorganic Chemistry"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44310-y","type":"journal-article","article-title":"IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity","volume":"15","author":"Landoni","year":"2024","journal-title":"Nature Communications"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2018.11.043","type":"journal-article","article-title":"Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma","volume":"176","author":"Li","year":"2019","journal-title":"Cell"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/s41586-023-06254-7","type":"journal-article","article-title":"Histone demethylase KDM5D upregulation drives sex differences in colon cancer","volume":"619","author":"Li","year":"2023","journal-title":"Nature"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010321","type":"journal-article","article-title":"Immunotherapy for triple-negative breast cancer: combination strategies to improve outcome","volume":"15","author":"Li","year":"2023","journal-title":"Cancers"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01929-1","type":"journal-article","article-title":"JAK\/STAT in leukemia: a clinical update","volume":"23","author":"Liang","year":"2024","journal-title":"Molecular Cancer"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35707-2","type":"journal-article","article-title":"The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis","volume":"13","author":"Lin","year":"2022","journal-title":"Nature Communications"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2018.02.052","type":"journal-article","article-title":"An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics","volume":"173","author":"Liu","year":"2018","journal-title":"Cell"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00487-x","type":"journal-article","article-title":"Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer","volume":"8","author":"Makhlin","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf1329","type":"journal-article","article-title":"Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients","volume":"384","author":"Mathew","year":"2024","journal-title":"Science"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04334-1","type":"journal-article","article-title":"Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity","volume":"9","author":"Nguyen","year":"2018","journal-title":"Nature Communications"},{"key":"bib39","first-page":"38","type":"journal-article","article-title":"Assessing the role of the interleukin-12\/STAT4 axis in breast cancer by a bioinformatics approach","volume":"48","author":"N\u00fa\u00f1ez-Marrero","year":"2019","journal-title":"International Journal of Sciences, Basic and Applied Research"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.immuni.2011.11.006","type":"journal-article","article-title":"Keeping STATs on memory CD8+ T cells","volume":"35","author":"Olson","year":"2011","journal-title":"Immunity"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11122002","type":"journal-article","article-title":"JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression","volume":"11","author":"Owen","year":"2019","journal-title":"Cancers"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107333","type":"journal-article","article-title":"A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast","volume":"40","author":"Pal","year":"2021","journal-title":"The EMBO Journal"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1111\/bjh.13373","type":"journal-article","article-title":"JAK1\/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms","volume":"169","author":"Parampalli Yajnanarayana","year":"2015","journal-title":"British Journal of Haematology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"523","DOI":"10.2147\/ITT.S485670","type":"journal-article","article-title":"JAK-STAT signaling in autoimmunity and cancer","volume":"14","author":"Parveen","year":"2025","journal-title":"ImmunoTargets and Therapy"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.trecan.2024.02.008","type":"journal-article","article-title":"The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments","volume":"10","author":"Rayson","year":"2024","journal-title":"Trends in Cancer"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abq6509","type":"journal-article","article-title":"CXCL9 and CXCL10 bring the heat to tumors","volume":"7","author":"Reschke","year":"2022","journal-title":"Science Immunology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41577-025-01255-1","type":"journal-article","article-title":"Inflame and restrain - the paradoxical roles of IL-12 and IL-23 in immunity","volume":"26","author":"Rindlisbacher","year":"2026","journal-title":"Nature Reviews. Immunology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1007-8","type":"journal-article","article-title":"Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups","volume":"567","author":"Rueda","year":"2019","journal-title":"Nature"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1158\/0008-5472.CAN-14-3198","type":"journal-article","article-title":"JAK inhibition impairs NK cell function in myeloproliferative neoplasms","volume":"75","author":"Sch\u00f6nberg","year":"2015","journal-title":"Cancer Research"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11111711","type":"journal-article","article-title":"STAT3 dysregulation in mature T and NK cell lymphomas","volume":"11","author":"Seffens","year":"2019","journal-title":"Cancers"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043","type":"journal-article","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1038\/s41591-019-0582-4","type":"journal-article","article-title":"Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study","volume":"25","author":"Staaf","year":"2019","journal-title":"Nature Medicine"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-018-0060-z","type":"journal-article","article-title":"Phase II study of ruxolitinib, a selective JAK1\/2 inhibitor, in patients with metastatic triple-negative breast cancer","volume":"4","author":"Stover","year":"2018","journal-title":"NPJ Breast Cancer"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cytogfr.2025.01.003","type":"journal-article","article-title":"Insights into IL-6\/JAK\/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy","volume":"85","author":"Thuya","year":"2025","journal-title":"Cytokine & Growth Factor Reviews"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1158\/1078-0432.CCR-24-2920","type":"journal-article","article-title":"Phase I Trial of TTI-101, a first-in-class oral inhibitor of STAT3, in patients with advanced solid tumors","volume":"31","author":"Tsimberidou","year":"2025","journal-title":"Clinical Cancer Research"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/eji.201948134","type":"journal-article","article-title":"The IL-12-STAT4 axis in the pathogenesis of human systemic lupus erythematosus","volume":"50","author":"Ueno","year":"2020","journal-title":"European Journal of Immunology"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/s41591-019-0432-4","type":"journal-article","article-title":"Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial","volume":"25","author":"Voorwerk","year":"2019","journal-title":"Nature Medicine"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54145-w","type":"journal-article","article-title":"Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications","volume":"15","author":"Wang","year":"2024","journal-title":"Nature Communications"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111846","type":"journal-article","article-title":"Deciphering JAK\/STAT signaling pathway: a multifaceted approach to tumorigenesis, progression and therapeutic interventions","volume":"131","author":"Wang","year":"2024","journal-title":"International Immunopharmacology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.0105-2896.2004.00211.x","type":"journal-article","article-title":"Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4","volume":"202","author":"Watford","year":"2004","journal-title":"Immunological Reviews"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.ccell.2022.05.005","type":"journal-article","article-title":"Redefining breast cancer subtypes to guide treatment prioritization and maximize response: predictive biomarkers across 10 cancer therapies","volume":"40","author":"Wolf","year":"2022","journal-title":"Cancer Cell"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","type":"journal-article","article-title":"A single-cell and spatially resolved atlas of human breast cancers","volume":"53","author":"Wu","year":"2021","journal-title":"Nature Genetics"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1007\/s11427-020-1714-8","type":"journal-article","article-title":"Triple-negative breast cancer: new treatment strategies in the era of precision medicine","volume":"64","author":"Wu","year":"2021","journal-title":"Science China. Life Sciences"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1038\/s41591-025-03776-7","type":"journal-article","article-title":"Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial","volume":"31","author":"Wu","year":"2025","journal-title":"Nature Medicine"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158352","type":"journal-article","article-title":"UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer","volume":"133","author":"Xiao","year":"2023","journal-title":"The Journal of Clinical Investigation"},{"key":"bib66","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1405491","type":"journal-article","article-title":"Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies","volume":"14","author":"Xiong","year":"2024","journal-title":"Frontiers in Oncology"},{"key":"bib67","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02108-4","type":"journal-article","article-title":"Breast cancer: pathogenesis and treatments","volume":"10","author":"Xiong","year":"2025","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.7150\/ijbs.41852","type":"journal-article","article-title":"STAT4: an immunoregulator contributing to diverse human diseases","volume":"16","author":"Yang","year":"2020","journal-title":"International Journal of Biological Sciences"},{"key":"bib69","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019561","type":"journal-article","article-title":"Exploring immune-related genes with prognostic value in microenvironment of breast cancer from TCGA database","volume":"99","author":"Yang","year":"2020","journal-title":"Medicine"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104861","type":"journal-article","article-title":"Effect of JAK\/STAT signaling on anti-PD-L1 immunotherapy efficacy in lung cancer","volume":"214","author":"Yao","year":"2025","journal-title":"Critical Reviews in Oncology\/Hematology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1158\/2326-6066.CIR-15-0014","type":"journal-article","article-title":"STAT3 in CD8+ T cells inhibits their tumor accumulation by downregulating CXCR3\/CXCL10 Axis","volume":"3","author":"Yue","year":"2015","journal-title":"Cancer Immunology Research"},{"key":"bib72","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade8520","type":"journal-article","article-title":"JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma","volume":"384","author":"Zak","year":"2024","journal-title":"Science"},{"key":"bib73","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2024.100910","type":"journal-article","article-title":"Enhancing immuno-oncology investigations through multidimensional decoding of tumor microenvironment with IOBR 2.0","volume":"4","author":"Zeng","year":"2024","journal-title":"Cell Reports Methods"},{"key":"bib74","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20181695","type":"journal-article","article-title":"Prognostic values of signal transducers activators of transcription in gastric cancer","volume":"39","author":"Zhang","year":"2019","journal-title":"Bioscience Reports"},{"key":"bib75","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02254-3","type":"journal-article","article-title":"Efficacy, safety and exploratory analysis of neoadjuvant tislelizumab (a PD-1 inhibitor) plus nab-paclitaxel followed by epirubicin\/cyclophosphamide for triple-negative breast cancer: a phase 2 TREND trial","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib76","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.886198","type":"journal-article","article-title":"Co-targeting tumor angiogenesis and immunosuppressive tumor microenvironment: a perspective in ethnopharmacology","volume":"13","author":"Zhou","year":"2022","journal-title":"Frontiers in Pharmacology"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.464","type":"journal-article","article-title":"STAT4 facilitates PD-L1 level via IL-12R\/JAK2\/STAT3 axis and predicts immunotherapy response in breast cancer","volume":"4","author":"Zhou","year":"2023","journal-title":"MedComm"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"943","DOI":"10.32604\/or.2023.044775","type":"journal-article","article-title":"Metochalcone induces senescence-associated secretory phenotype via JAK2\/STAT3 pathway in breast cancer","volume":"32","author":"Zhou","year":"2024","journal-title":"Oncology Research"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1515\/jtim-2025-0093","type":"journal-article","article-title":"Co-targeting ferroptosis and immune evasion through small molecules in breast cancer","volume":"13","author":"Zhou","year":"2025","journal-title":"Journal of Translational Internal Medicine"},{"key":"bib80","type":"software","article-title":"2025-JAK-STAT-breast-cancer","author":"Zhou","year":"2026","unstructured":"Zhou J. 2026. 2025-JAK-STAT-breast-cancer. Software Heritage. swh:1:rev:cc493a8367ef788330266d38098adb22358f2a46. https:\/\/archive.softwareheritage.org\/swh:1:dir:2973c64febd3c15009dccfd3622cbf7ae012218c;origin=https:\/\/github.com\/Jianbo1999\/2025-JAK-STAT-breast-cancer;visit=swh:1:snp:4d4ff7541c10e8dc2ce373cc59d8310f655b7d86;anchor=swh:1:rev:cc493a8367ef788330266d38098adb22358f2a46."},{"key":"dataset1","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.33780247","type":"dataset","article-title":"Raw sequencing data and raw IHC image data","volume-title":"figshare","author":"Zhou","year":"2026","unstructured":"Zhou J. 2026. Raw sequencing data and raw IHC image data. figshare."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/110635\/elife-110635-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/110635\/elife-110635-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/110635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:35:47Z","timestamp":1791873347000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/110635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":81,"alternative-id":["10.7554\/eLife.110635"],"URL":"https:\/\/doi.org\/10.7554\/elife.110635","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.64898\/2026.02.03.703506","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.110635.4","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.110635.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.110635.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.110635.3","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33780247","asserted-by":"subject"},{"id-type":"uri","id":"https:\/\/archive.softwareheritage.org\/swh:1:dir:2973c64febd3c15009dccfd3622cbf7ae012218c;origin=https:\/\/github.com\/Jianbo1999\/2025-JAK-STAT-breast-cancer;visit=swh:1:snp:4d4ff7541c10e8dc2ce373cc59d8310f655b7d86;anchor=swh:1:rev:cc493a8367ef788330266d38098adb22358f2a46","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP110635"}}