{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:00:19Z","timestamp":1785776419144,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,31]]},"group-title":"Cancer Biology","reference-count":103,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA193837"],"award-info":[{"award-number":["CA193837"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA092629"],"award-info":[{"award-number":["CA092629"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA265768"],"award-info":[{"award-number":["CA265768"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA008748"],"award-info":[{"award-number":["CA008748"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32GM152349"],"award-info":[{"award-number":["T32GM152349"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Despite considerable progress in elucidating mechanisms leading to castration-resistant prostate cancer (CRPC), insight into the early stages of prostate cancer initiation and progression remains limited. Genomic drivers of prostate cancer initiation have been defined through patient tumor sequencing, but the subsequent events responsible for local tissue invasion are poorly understood. Here we leverage a well-studied genetically engineered mouse prostate cancer model (Hi-Myc) that, based on robust and reproducible kinetics for transitioning from pre-invasive prostatic intraepithelial neoplasia (PIN) to invasive prostate adenocarcinoma (PCa), provides an ideal system to systematically address this question using single-cell analysis. Surprisingly, the transcriptomic profiles of early PIN lesions are indistinguishable from those of late-stage, highly invasive tumor cells, suggesting that MYC activation at the PIN stage establishes a transcriptional program that is fully capable of driving invasion but is restrained by the local tumor microenvironment (TME). Indeed, we find that progression to PCa is associated with progressive infiltration of IL-1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  tumor-infiltrating macrophages at the PIN stage that, based on immunodepletion and cytokine neutralization experiments, are required for the PIN-to-PCa transition. Mechanistically, IL-1\u03b2 from macrophages acts directly on prostate fibroblasts, leading to the release of IL-6, which drives invasion by activating IL-6R in tumor cells. Collectively, these findings identify a pro-tumorigenic IL-1\u03b2\/IL-6 signaling circuit mediated through local macrophages and fibroblasts that unleashes the full oncogenic potential of a cancer driver (MYC) activated at the PIN stage. We also find evidence of this circuit in other (non-MYC-driven) prostate cancer models as well as human prostate and lung adenocarcinoma, with implications for TME-specific targeted therapeutics in early-stage disease.\n                <\/jats:p>","DOI":"10.64898\/2026.07.30.741572","type":"posted-content","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:35:11Z","timestamp":1785508511000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-1\u03b2\/IL-6 signaling circuit in the tumor microenvironment drives prostate cancer development"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-7341","authenticated-orcid":false,"given":"Young Sun","family":"Lee","sequence":"first","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy L.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Chryplewicz","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Land","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Chan","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perianne","family":"Smith","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kottapalli","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Fong","sequence":"additional","affiliation":[{"name":"Calico Life Sciences LLC, San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"Chen","sequence":"additional","affiliation":[{"name":"Calico Life Sciences LLC, San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bent","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Department of Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HuiYong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"de Stanchina","sequence":"additional","affiliation":[{"name":"Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfei","family":"Kang","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shevin","family":"Narine","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rosiek","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Fan","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erolcan","family":"Sayar","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Gopalan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ojasvi","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Xu","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignas","family":"Masilionis","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Chaligne","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Haffner","sequence":"additional","affiliation":[{"name":"Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Romero","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Pe\u2019er","sequence":"additional","affiliation":[{"name":"Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett S.","family":"Carver","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-6475","authenticated-orcid":false,"given":"Charles L.","family":"Sawyers","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080309361699000_2026.07.30.741572v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nm972"},{"key":"2026080309361699000_2026.07.30.741572v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505253322101"},{"key":"2026080309361699000_2026.07.30.741572v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/76287"},{"key":"2026080309361699000_2026.07.30.741572v1.4","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3630"},{"key":"2026080309361699000_2026.07.30.741572v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.09.031"},{"key":"2026080309361699000_2026.07.30.741572v1.6","unstructured":"Nickerson, T. et al. In Vivo Progression of LAPC-9 and LNCaP Prostate Cancer Models to Androgen Independence Is Associated with Increased Expression of Insulin-like Growth Factor I (IGF-I) and IGF-I Receptor (IGF-IR)."},{"key":"2026080309361699000_2026.07.30.741572v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-401"},{"key":"2026080309361699000_2026.07.30.741572v1.8","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4000"},{"key":"2026080309361699000_2026.07.30.741572v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107898108"},{"key":"2026080309361699000_2026.07.30.741572v1.10","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1038\/s43018-024-00838-6","article-title":"The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1","volume":"5","year":"2024","journal-title":"Nat. Cancer"},{"key":"2026080309361699000_2026.07.30.741572v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn0478"},{"key":"2026080309361699000_2026.07.30.741572v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.005"},{"key":"2026080309361699000_2026.07.30.741572v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0266-0"},{"key":"2026080309361699000_2026.07.30.741572v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.025"},{"key":"2026080309361699000_2026.07.30.741572v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2279"},{"key":"2026080309361699000_2026.07.30.741572v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature09744"},{"key":"2026080309361699000_2026.07.30.741572v1.17","doi-asserted-by":"crossref","unstructured":"Tomlins, S. A. et al. Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer. 310, (2005).","DOI":"10.1126\/science.1117679"},{"key":"2026080309361699000_2026.07.30.741572v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0086-z"},{"key":"2026080309361699000_2026.07.30.741572v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65054-7"},{"key":"2026080309361699000_2026.07.30.741572v1.20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.pathmechdis.3.121806.154305","article-title":"Pancreatic Cancer","volume":"3","year":"2008","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"2026080309361699000_2026.07.30.741572v1.21","unstructured":"Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse."},{"key":"2026080309361699000_2026.07.30.741572v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023"},{"key":"2026080309361699000_2026.07.30.741572v1.23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198809013190901"},{"key":"2026080309361699000_2026.07.30.741572v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"2026080309361699000_2026.07.30.741572v1.25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282001"},{"key":"2026080309361699000_2026.07.30.741572v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.01.012"},{"key":"2026080309361699000_2026.07.30.741572v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"2026080309361699000_2026.07.30.741572v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature07205"},{"key":"2026080309361699000_2026.07.30.741572v1.29","unstructured":"Uemura, N. , Yamaguchi, S. & Schlemper, R. J . Helicobacter pylori Infection and the Development of Gastric Cancer. N. Engl. J. Med."},{"key":"2026080309361699000_2026.07.30.741572v1.30","unstructured":"Correa, P. Human Gastric Carcinogenesis: A Multistep and Multifactorial Process First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention."},{"key":"2026080309361699000_2026.07.30.741572v1.31","unstructured":"Eaden, J. A. , Abrams, K. R. & Mayberry, J. F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. G."},{"key":"2026080309361699000_2026.07.30.741572v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2025.12.049"},{"key":"2026080309361699000_2026.07.30.741572v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03147-x"},{"key":"2026080309361699000_2026.07.30.741572v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.06.020"},{"key":"2026080309361699000_2026.07.30.741572v1.35","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.stem.2025.01.011","article-title":"Sustained NF-\u03baB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation","volume":"32","year":"2025","journal-title":"Cell Stem Cell"},{"key":"2026080309361699000_2026.07.30.741572v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.add5327"},{"key":"2026080309361699000_2026.07.30.741572v1.37","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-24-0060"},{"key":"2026080309361699000_2026.07.30.741572v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08290-3"},{"key":"2026080309361699000_2026.07.30.741572v1.39","doi-asserted-by":"crossref","unstructured":"Hirz, T. et al. Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses. Nat. Commun. 14, 663 (2023).","DOI":"10.1038\/s41467-023-36325-2"},{"key":"2026080309361699000_2026.07.30.741572v1.40","doi-asserted-by":"crossref","unstructured":"Song, H. et al. Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states. Nat. Commun. 13, 141 (2022).","DOI":"10.1038\/s41467-021-27322-4"},{"key":"2026080309361699000_2026.07.30.741572v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65517-4"},{"key":"2026080309361699000_2026.07.30.741572v1.42","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/s41423-025-01358-8","article-title":"IL-1 family cytokines in inflammation and immunity","volume":"22","year":"2025","journal-title":"Cell. Mol. Immunol"},{"key":"2026080309361699000_2026.07.30.741572v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.012"},{"key":"2026080309361699000_2026.07.30.741572v1.44","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00910"},{"key":"2026080309361699000_2026.07.30.741572v1.45","doi-asserted-by":"crossref","unstructured":"Lee, J. M. et al. CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB\u2013IIIA NSCLC. JTO Clin. Res. Rep. 6, 100859 (2025).","DOI":"10.1016\/j.jtocrr.2025.100859"},{"key":"2026080309361699000_2026.07.30.741572v1.46","doi-asserted-by":"crossref","unstructured":"Paz-Ares, L. et al. Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial. Lung Cancer 189, 107451 (2024).","DOI":"10.1016\/j.lungcan.2023.107451"},{"key":"2026080309361699000_2026.07.30.741572v1.47","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1200\/JCO.23.00980","article-title":"Canakinumab Versus Placebo in Combination With First-Line Pembrolizumab Plus Chemotherapy for Advanced Non\u2013Small-Cell Lung Cancer: Results From the CANOPY-1 Trial","volume":"42","year":"2024","journal-title":"J. Clin. Oncol"},{"key":"2026080309361699000_2026.07.30.741572v1.48","doi-asserted-by":"crossref","unstructured":"Ellwood-Yen, K. et al. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. CANCER CELL (2003).","DOI":"10.1002\/0471675067.mmc008"},{"key":"2026080309361699000_2026.07.30.741572v1.49","doi-asserted-by":"crossref","unstructured":"Kalkat, M. et al. MYC Deregulation in Primary Human Cancers. Genes 8, 151 (2017).","DOI":"10.3390\/genes8060151"},{"key":"2026080309361699000_2026.07.30.741572v1.50","doi-asserted-by":"crossref","unstructured":"Casacuberta-Serra, S. , Gonz\u00e1lez-Larreategui, \u00cd. , Capit\u00e1n-Leo, D. & Soucek, L . MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer. Signal Transduct. Target. Ther. 9, 205 (2024).","DOI":"10.1038\/s41392-024-01907-z"},{"key":"2026080309361699000_2026.07.30.741572v1.51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009427"},{"key":"2026080309361699000_2026.07.30.741572v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30257-z"},{"key":"2026080309361699000_2026.07.30.741572v1.53","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1038\/s41388-020-01389-7","article-title":"MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity","volume":"39","year":"2020","journal-title":"Oncogene"},{"key":"2026080309361699000_2026.07.30.741572v1.54","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0124"},{"key":"2026080309361699000_2026.07.30.741572v1.55","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0519"},{"key":"2026080309361699000_2026.07.30.741572v1.56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63324"},{"key":"2026080309361699000_2026.07.30.741572v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.236"},{"key":"2026080309361699000_2026.07.30.741572v1.58","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030411"},{"key":"2026080309361699000_2026.07.30.741572v1.59","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay0267"},{"key":"2026080309361699000_2026.07.30.741572v1.60","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59465"},{"key":"2026080309361699000_2026.07.30.741572v1.61","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1038\/s41588-025-02289-w","article-title":"ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L","volume":"57","year":"2025","journal-title":"Nat. Genet"},{"key":"2026080309361699000_2026.07.30.741572v1.62","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79076"},{"key":"2026080309361699000_2026.07.30.741572v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/nature13638"},{"key":"2026080309361699000_2026.07.30.741572v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06696-z"},{"key":"2026080309361699000_2026.07.30.741572v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06685-2"},{"key":"2026080309361699000_2026.07.30.741572v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03651-8"},{"key":"2026080309361699000_2026.07.30.741572v1.67","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41586-025-09493-y","article-title":"Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours","volume":"646","year":"2025","journal-title":"Nature"},{"key":"2026080309361699000_2026.07.30.741572v1.68","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s43018-020-00148-7","article-title":"Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer","volume":"2","year":"2020","journal-title":"Nat. Cancer"},{"key":"2026080309361699000_2026.07.30.741572v1.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.06.018"},{"key":"2026080309361699000_2026.07.30.741572v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.014"},{"key":"2026080309361699000_2026.07.30.741572v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01475-4"},{"key":"2026080309361699000_2026.07.30.741572v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.032"},{"key":"2026080309361699000_2026.07.30.741572v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.015"},{"key":"2026080309361699000_2026.07.30.741572v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109844"},{"key":"2026080309361699000_2026.07.30.741572v1.75","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf7777"},{"key":"2026080309361699000_2026.07.30.741572v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.02.021"},{"key":"2026080309361699000_2026.07.30.741572v1.77","doi-asserted-by":"crossref","first-page":"eabg7504","DOI":"10.1126\/scitranslmed.abg7504","article-title":"Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics","volume":"14","year":"2022","journal-title":"Sci. Transl. Med"},{"key":"2026080309361699000_2026.07.30.741572v1.78","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1158\/1541-7786.MCR-24-0791","article-title":"Single-Cell and Spatial Transcriptomics Reveal a Tumor-Associated Macrophage Subpopulation that Mediates Prostate Cancer Progression and Metastasis","volume":"23","year":"2025","journal-title":"Mol. Cancer Res"},{"key":"2026080309361699000_2026.07.30.741572v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05874-3"},{"key":"2026080309361699000_2026.07.30.741572v1.80","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccell.2025.10.004","article-title":"Multimodal spatial-omics reveal co-evolution of alveolar progenitors and proinflammatory niches in progression of lung precursor lesions","volume":"44","year":"2026","journal-title":"Cancer Cell"},{"key":"2026080309361699000_2026.07.30.741572v1.81","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63067-2"},{"key":"2026080309361699000_2026.07.30.741572v1.82","unstructured":"Libermann, T. A. & Baltimore, D . Activation of Interleukin-6 Gene Expression through the NF-KB Transcription Factor. MOL CELL BIOL."},{"key":"2026080309361699000_2026.07.30.741572v1.83","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.8"},{"key":"2026080309361699000_2026.07.30.741572v1.84","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295"},{"key":"2026080309361699000_2026.07.30.741572v1.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.06.046"},{"key":"2026080309361699000_2026.07.30.741572v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)32247-x"},{"key":"2026080309361699000_2026.07.30.741572v1.87","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39953-w"},{"key":"2026080309361699000_2026.07.30.741572v1.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.033"},{"key":"2026080309361699000_2026.07.30.741572v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.73"},{"key":"2026080309361699000_2026.07.30.741572v1.90","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.09.005"},{"key":"2026080309361699000_2026.07.30.741572v1.91","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-3122"},{"key":"2026080309361699000_2026.07.30.741572v1.92","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0855"},{"key":"2026080309361699000_2026.07.30.741572v1.93","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2603878"},{"key":"2026080309361699000_2026.07.30.741572v1.94","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2413361"},{"key":"2026080309361699000_2026.07.30.741572v1.95","doi-asserted-by":"crossref","unstructured":"Svensson, E. C. , et al. TET2 -Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial. JAMA Cardiol. 7, 521 (2022).","DOI":"10.1001\/jamacardio.2022.0386"},{"key":"2026080309361699000_2026.07.30.741572v1.96","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1016\/j.cell.2026.05.005","article-title":"Plasma signals of lung tumor promotion for molecular cancer prevention","volume":"189","year":"2026","journal-title":"Cell"},{"key":"2026080309361699000_2026.07.30.741572v1.97","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3441"},{"key":"2026080309361699000_2026.07.30.741572v1.98","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0710"},{"key":"2026080309361699000_2026.07.30.741572v1.99","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"2026080309361699000_2026.07.30.741572v1.100","doi-asserted-by":"crossref","unstructured":"Gao, J. et al. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal. Sci. Signal. 6, (2013).","DOI":"10.1126\/scisignal.2004088"},{"key":"2026080309361699000_2026.07.30.741572v1.101","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"2026080309361699000_2026.07.30.741572v1.102","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110344118"},{"key":"2026080309361699000_2026.07.30.741572v1.103","doi-asserted-by":"crossref","unstructured":"Akama-Garren, E. H. et al. A Modular Assembly Platform for Rapid Generation of DNA Constructs. Sci. Rep. 6, 16836 (2016).","DOI":"10.1038\/srep16836"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.30.741572","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:36:26Z","timestamp":1785774986000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.30.741572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":103,"URL":"https:\/\/doi.org\/10.64898\/2026.07.30.741572","relation":{},"subject":[],"published":{"date-parts":[[2026,7,31]]},"subtype":"preprint"}}