{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:45:30Z","timestamp":1794282330289,"version":"4.9.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["Noncommunicable Chronic Diseases-National Science and Technology Major Project"],"award-info":[{"award-number":["Noncommunicable Chronic Diseases-National Science and Technology Major Project"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"DOI":"10.1186\/s12943-025-02497-2","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:58:01Z","timestamp":1764223081000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Senescent SPP1+ macrophages remodel the tumor microenvironment and promote the progression of early-stage lung adenocarcinoma featured with mixed ground glass nodule"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-4541","authenticated-orcid":false,"given":"Hong","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha-sha","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-feng","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-bing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3699-8138","authenticated-orcid":false,"given":"Ji-gang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"2497_CR1","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1016\/j.jtho.2018.05.006","volume":"13","author":"JE Walter","year":"2018","unstructured":"Walter JE, et al. New subsolid pulmonary nodules in lung cancer screening: the NELSON trial. J Thorac Oncol. 2018;13:1410\u20134. https:\/\/doi.org\/10.1016\/j.jtho.2018.05.006.","journal-title":"J Thorac Oncol"},{"key":"2497_CR2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/med4.38","volume":"1","author":"Z Qiu","year":"2023","unstructured":"Qiu Z, et al. Proteomic characteristics of lung adenocarcinoma tumors that are small but highly invasive. Med Adv. 2023;1:340\u201352. https:\/\/doi.org\/10.1002\/med4.38.","journal-title":"Med Adv"},{"key":"2497_CR3","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1016\/j.jtho.2019.08.002","volume":"14","author":"F Fu","year":"2019","unstructured":"Fu F, et al. Distinct prognostic factors in patients with stage I Non-Small cell lung cancer with radiologic Part-Solid or solid lesions. J Thorac Oncol. 2019;14:2133\u201342. https:\/\/doi.org\/10.1016\/j.jtho.2019.08.002.","journal-title":"J Thorac Oncol"},{"key":"2497_CR4","doi-asserted-by":"publisher","first-page":"4584","DOI":"10.21037\/jtd-20-1972","volume":"12","author":"L Qi","year":"2020","unstructured":"Qi L, et al. Persistent pulmonary subsolid nodules with a solid component smaller than 6\u00a0mm: what do we know? J Thorac Dis. 2020;12:4584\u20137. https:\/\/doi.org\/10.21037\/jtd-20-1972.","journal-title":"J Thorac Dis"},{"key":"2497_CR5","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1148\/radiol.2017161659","volume":"284","author":"H MacMahon","year":"2017","unstructured":"MacMahon H, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner society 2017. Radiology. 2017;284:228\u201343. https:\/\/doi.org\/10.1148\/radiol.2017161659.","journal-title":"Radiology"},{"key":"2497_CR6","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.jtho.2016.03.025","volume":"11","author":"WD Travis","year":"2016","unstructured":"Travis WD, et al. The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in Part-Solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2016;11:1204\u201323. https:\/\/doi.org\/10.1016\/j.jtho.2016.03.025.","journal-title":"J Thorac Oncol"},{"key":"2497_CR7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41421-020-00200-x","volume":"6","author":"T Lu","year":"2020","unstructured":"Lu T, et al. Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules. Cell Discov. 2020;6:69. https:\/\/doi.org\/10.1038\/s41421-020-00200-x.","journal-title":"Cell Discov"},{"key":"2497_CR8","doi-asserted-by":"publisher","unstructured":"Xing X, et al. Decoding the multicellular ecosystem of lung adenocarcinoma manifested as pulmonary subsolid nodules by single-cell RNA sequencing. Sci Adv. 2021;7. https:\/\/doi.org\/10.1126\/sciadv.abd9738.","DOI":"10.1126\/sciadv.abd9738"},{"key":"2497_CR9","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/s41568-022-00547-1","volume":"23","author":"L Cassetta","year":"2023","unstructured":"Cassetta L, et al. A timeline of tumour-associated macrophage biology. Nat Rev Cancer. 2023;23:238\u201357. https:\/\/doi.org\/10.1038\/s41568-022-00547-1.","journal-title":"Nat Rev Cancer"},{"key":"2497_CR10","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41586-020-2316-7","volume":"582","author":"Z Bian","year":"2020","unstructured":"Bian Z, et al. Deciphering human macrophage development at single-cell resolution. Nature. 2020;582:571\u20136. https:\/\/doi.org\/10.1038\/s41586-020-2316-7.","journal-title":"Nature"},{"key":"2497_CR11","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/s41586-021-03651-8","volume":"595","author":"M Casanova-Acebes","year":"2021","unstructured":"Casanova-Acebes M, et al. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells. Nature. 2021;595:578\u201384. https:\/\/doi.org\/10.1038\/s41586-021-03651-8.","journal-title":"Nature"},{"key":"2497_CR12","doi-asserted-by":"publisher","first-page":"215667","DOI":"10.1016\/j.canlet.2022.215667","volume":"537","author":"C Shang","year":"2022","unstructured":"Shang C, et al. CXCL10 conditions alveolar macrophages within the premetastatic niche to promote metastasis. Cancer Lett. 2022;537:215667. https:\/\/doi.org\/10.1016\/j.canlet.2022.215667.","journal-title":"Cancer Lett"},{"key":"2497_CR13","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.it.2020.08.008","volume":"41","author":"J Kulikauskaite","year":"2020","unstructured":"Kulikauskaite J, et al. Teaching old dogs new tricks? The plasticity of lung alveolar macrophage subsets. Trends Immunol. 2020;41:864\u201377. https:\/\/doi.org\/10.1016\/j.it.2020.08.008.","journal-title":"Trends Immunol"},{"key":"2497_CR14","doi-asserted-by":"publisher","unstructured":"Guo Y, et al. Zeb1 induces immune checkpoints to form an immunosuppressive envelope around invading cancer cells. Sci Adv. 2021;7. https:\/\/doi.org\/10.1126\/sciadv.abd7455.","DOI":"10.1126\/sciadv.abd7455"},{"key":"2497_CR15","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1007\/s00262-022-03173-w","volume":"71","author":"H Zhang","year":"2022","unstructured":"Zhang H, et al. Immunosuppressive TREM2(+) macrophages are associated with undesirable prognosis and responses to anti-PD-1 immunotherapy in non-small cell lung cancer. Cancer Immunol Immunother. 2022;71:2511\u201322. https:\/\/doi.org\/10.1007\/s00262-022-03173-w.","journal-title":"Cancer Immunol Immunother"},{"key":"2497_CR16","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41392-022-01130-8","volume":"7","author":"C Wang","year":"2022","unstructured":"Wang C, et al. The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing. Signal Transduct Target Ther. 2022;7:289. https:\/\/doi.org\/10.1038\/s41392-022-01130-8.","journal-title":"Signal Transduct Target Ther"},{"key":"2497_CR17","doi-asserted-by":"publisher","unstructured":"Matsubara E, et al. SPP1 derived from macrophages is associated with a worse clinical course and Chemo-Resistance in lung adenocarcinoma. Cancers (Basel). 2022;14. https:\/\/doi.org\/10.3390\/cancers14184374.","DOI":"10.3390\/cancers14184374"},{"key":"2497_CR18","doi-asserted-by":"publisher","unstructured":"Li Y, et al. Single-cell RNA sequencing reveals the multi\u2010cellular ecosystem in different radiological components of pulmonary part\u2010solid nodules. Clin Transl Med. 2022;12. https:\/\/doi.org\/10.1002\/ctm2.723.","DOI":"10.1002\/ctm2.723"},{"key":"2497_CR19","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s12943-024-02177-7","volume":"23","author":"YF Ren","year":"2024","unstructured":"Ren YF, et al. Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma. Mol Cancer. 2024;23:263. https:\/\/doi.org\/10.1186\/s12943-024-02177-7.","journal-title":"Mol Cancer"},{"key":"2497_CR20","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1097\/JTO.0b013e318206a221","volume":"6","author":"WD Travis","year":"2011","unstructured":"Travis WD, et al. International association for the study of lung cancer\/american thoracic society\/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244\u201385. https:\/\/doi.org\/10.1097\/JTO.0b013e318206a221.","journal-title":"J Thorac Oncol"},{"key":"2497_CR21","doi-asserted-by":"publisher","first-page":"e2100752","DOI":"10.1002\/smtd.202100752","volume":"6","author":"K Jin","year":"2022","unstructured":"Jin K, et al. Single-Cell RNA sequencing reveals the Temporal diversity and dynamics of cardiac immunity after myocardial infarction. Small Methods. 2022;6:e2100752. https:\/\/doi.org\/10.1002\/smtd.202100752.","journal-title":"Small Methods"},{"key":"2497_CR22","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41586-018-0694-x","volume":"564","author":"L Zhang","year":"2018","unstructured":"Zhang L, et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature. 2018;564:268\u201372. https:\/\/doi.org\/10.1038\/s41586-018-0694-x.","journal-title":"Nature"},{"key":"2497_CR23","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1038\/s41591-018-0096-5","volume":"24","author":"D Lambrechts","year":"2018","unstructured":"Lambrechts D, et al. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med. 2018;24:1277\u201389. https:\/\/doi.org\/10.1038\/s41591-018-0096-5.","journal-title":"Nat Med"},{"key":"2497_CR24","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1038\/s41467-020-16164-1","volume":"11","author":"N Kim","year":"2020","unstructured":"Kim N, et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun. 2020;11:2285. https:\/\/doi.org\/10.1038\/s41467-020-16164-1.","journal-title":"Nat Commun"},{"key":"2497_CR25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cellimm.2018.01.020","volume":"330","author":"A Remmerie","year":"2018","unstructured":"Remmerie A, et al. Macrophages and lipid metabolism. Cell Immunol. 2018;330:27\u201342. https:\/\/doi.org\/10.1016\/j.cellimm.2018.01.020.","journal-title":"Cell Immunol"},{"key":"2497_CR26","doi-asserted-by":"publisher","unstructured":"Villani AC, et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 2017;356. https:\/\/doi.org\/10.1126\/science.aah4573.","DOI":"10.1126\/science.aah4573"},{"key":"2497_CR27","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/s00262-017-2023-x","volume":"66","author":"W van der Touw","year":"2017","unstructured":"van der Touw W, et al. LILRB receptor-mediated regulation of myeloid cell maturation and function. Cancer Immunol Immunother. 2017;66:1079\u201387. https:\/\/doi.org\/10.1007\/s00262-017-2023-x.","journal-title":"Cancer Immunol Immunother"},{"key":"2497_CR28","doi-asserted-by":"publisher","first-page":"109674","DOI":"10.1016\/j.celrep.2021.109674","volume":"36","author":"X He","year":"2021","unstructured":"He X, et al. Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche. Cell Rep. 2021;36:109674. https:\/\/doi.org\/10.1016\/j.celrep.2021.109674.","journal-title":"Cell Rep"},{"key":"2497_CR29","doi-asserted-by":"publisher","first-page":"6619","DOI":"10.1038\/s41467-022-34395-2","volume":"13","author":"H Luo","year":"2022","unstructured":"Luo H, et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment. Nat Commun. 2022;13:6619. https:\/\/doi.org\/10.1038\/s41467-022-34395-2.","journal-title":"Nat Commun"},{"key":"2497_CR30","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","volume":"20","author":"AM van der Leun","year":"2020","unstructured":"van der Leun AM, et al. CD8(+) T cell States in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020;20:218\u201332. https:\/\/doi.org\/10.1038\/s41568-019-0235-4.","journal-title":"Nat Rev Cancer"},{"key":"2497_CR31","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1126\/science.aaf0683","volume":"355","author":"AO Kamphorst","year":"2017","unstructured":"Kamphorst AO, et al. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science. 2017;355:1423\u20137. https:\/\/doi.org\/10.1126\/science.aaf0683.","journal-title":"Science"},{"key":"2497_CR32","doi-asserted-by":"publisher","first-page":"e149","DOI":"10.1002\/ctm2.149","volume":"10","author":"F Wu","year":"2020","unstructured":"Wu F, et al. Synchronous ground-glass nodules showed limited response to anti-PD-1\/PD-L1 therapy in patients with advanced lung adenocarcinoma. Clin Transl Med. 2020;10:e149. https:\/\/doi.org\/10.1002\/ctm2.149.","journal-title":"Clin Transl Med"},{"key":"2497_CR33","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.immuni.2017.11.021","volume":"47","author":"K Man","year":"2017","unstructured":"Man K, et al. Transcription factor IRF4 promotes CD8(+) T cell exhaustion and limits the development of Memory-like T cells during chronic infection. Immunity. 2017;47:1129\u201341. https:\/\/doi.org\/10.1016\/j.immuni.2017.11.021.","journal-title":"Immunity"},{"key":"2497_CR34","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41590-020-00850-9","volume":"22","author":"Y Liu","year":"2021","unstructured":"Liu Y, et al. IL-2 regulates tumor-reactive CD8(+) T cell exhaustion by activating the Aryl hydrocarbon receptor. Nat Immunol. 2021;22:358\u201369. https:\/\/doi.org\/10.1038\/s41590-020-00850-9.","journal-title":"Nat Immunol"},{"key":"2497_CR35","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.4049\/jimmunol.1200593","volume":"190","author":"J Bae","year":"2013","unstructured":"Bae J, et al. Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells. J Immunol. 2013;190:1360\u201371. https:\/\/doi.org\/10.4049\/jimmunol.1200593.","journal-title":"J Immunol"},{"key":"2497_CR36","doi-asserted-by":"publisher","first-page":"454","DOI":"10.3389\/fimmu.2019.00454","volume":"10","author":"M Shevtsov","year":"2019","unstructured":"Shevtsov M, et al. Ex vivo Hsp70-Activated NK cells in combination with PD-1 Inhibition significantly increase overall survival in preclinical models of glioblastoma and lung cancer. Front Immunol. 2019;10:454. https:\/\/doi.org\/10.3389\/fimmu.2019.00454.","journal-title":"Front Immunol"},{"key":"2497_CR37","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","volume":"577","author":"BA Helmink","year":"2020","unstructured":"Helmink BA, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577:549\u201355. https:\/\/doi.org\/10.1038\/s41586-019-1922-8.","journal-title":"Nature"},{"key":"2497_CR38","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1164\/rccm.201309-1611OC","volume":"189","author":"C Germain","year":"2014","unstructured":"Germain C, et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am J Respir Crit Care Med. 2014;189:832\u201344. https:\/\/doi.org\/10.1164\/rccm.201309-1611OC.","journal-title":"Am J Respir Crit Care Med"},{"key":"2497_CR39","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.immuni.2018.12.027","volume":"50","author":"B Reizis","year":"2019","unstructured":"Reizis B. Plasmacytoid dendritic cells: Development, Regulation, and function. Immunity. 2019;50:37\u201350. https:\/\/doi.org\/10.1016\/j.immuni.2018.12.027.","journal-title":"Immunity"},{"key":"2497_CR40","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.ccell.2023.05.006","volume":"41","author":"LI Prieto","year":"2023","unstructured":"Prieto LI, et al. Senescent alveolar macrophages promote early-stage lung tumorigenesis. Cancer Cell. 2023;41:1261\u201375. https:\/\/doi.org\/10.1016\/j.ccell.2023.05.006.","journal-title":"Cancer Cell"},{"key":"2497_CR41","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.acra.2018.12.002","volume":"26","author":"L Fan","year":"2019","unstructured":"Fan L, et al. Lung cancer screening with Low-Dose CT: baseline screening results in Shanghai. Acad Radiol. 2019;26:1283\u201391. https:\/\/doi.org\/10.1016\/j.acra.2018.12.002.","journal-title":"Acad Radiol"},{"key":"2497_CR42","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1148\/radiol.2019190905","volume":"293","author":"MM Hammer","year":"2019","unstructured":"Hammer MM, et al. Cancer risk in subsolid nodules in the National lung screening trial. Radiology. 2019;293:441\u20138. https:\/\/doi.org\/10.1148\/radiol.2019190905.","journal-title":"Radiology"},{"key":"2497_CR43","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1056\/NEJMoa1911793","volume":"382","author":"HJ de Koning","year":"2020","unstructured":"de Koning HJ, et al. Reduced Lung-Cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382:503\u201313. https:\/\/doi.org\/10.1056\/NEJMoa1911793.","journal-title":"N Engl J Med"},{"key":"2497_CR44","doi-asserted-by":"publisher","first-page":"6500","DOI":"10.1038\/s41467-021-26770-2","volume":"12","author":"Z Wang","year":"2021","unstructured":"Wang Z, et al. Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing. Nat Commun. 2021;12:6500. https:\/\/doi.org\/10.1038\/s41467-021-26770-2.","journal-title":"Nat Commun"},{"key":"2497_CR45","doi-asserted-by":"publisher","first-page":"e2205462","DOI":"10.1002\/advs.202205462","volume":"10","author":"M Wu","year":"2023","unstructured":"Wu M, et al. Promotion of lung cancer metastasis by SIRT2-Mediated extracellular protein deacetylation. Adv Sci (Weinh). 2023;10:e2205462. https:\/\/doi.org\/10.1002\/advs.202205462.","journal-title":"Adv Sci (Weinh)"},{"key":"2497_CR46","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/s41419-022-05336-0","volume":"13","author":"X Rao","year":"2022","unstructured":"Rao X, et al. NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer. Cell Death Dis. 2022;13:891. https:\/\/doi.org\/10.1038\/s41419-022-05336-0.","journal-title":"Cell Death Dis"},{"key":"2497_CR47","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1016\/j.cmet.2021.09.002","volume":"33","author":"SM Morrissey","year":"2021","unstructured":"Morrissey SM, et al. Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming. Cell Metab. 2021;33:2040\u201358. https:\/\/doi.org\/10.1016\/j.cmet.2021.09.002.","journal-title":"Cell Metab"},{"key":"2497_CR48","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1158\/2326-6066.CIR-22-0547","volume":"11","author":"K He","year":"2023","unstructured":"He K, et al. Inhibition of STAT6 with antisense oligonucleotides enhances the systemic antitumor effects of radiotherapy and Anti-PD-1 in metastatic Non-Small cell lung cancer. Cancer Immunol Res. 2023;11:486\u2013500.https:\/\/doi.org\/10.1158\/2326-6066.CIR-22-0547.","journal-title":"Cancer Immunol Res"},{"key":"2497_CR49","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1158\/0008-5472.CAN-20-1885","volume":"81","author":"L La Fleur","year":"2021","unstructured":"La Fleur L, et al. Targeting MARCO and IL37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function. Cancer Res. 2021;81:956\u201367. https:\/\/doi.org\/10.1158\/0008-5472.CAN-20-1885.","journal-title":"Cancer Res"},{"key":"2497_CR50","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41591-021-01625-x","volume":"28","author":"J Theruvath","year":"2022","unstructured":"Theruvath J, et al. Anti-GD2 synergizes with CD47 Blockade to mediate tumor eradication. Nat Med. 2022;28:333\u201344. https:\/\/doi.org\/10.1038\/s41591-021-01625-x.","journal-title":"Nat Med"},{"key":"2497_CR51","doi-asserted-by":"publisher","first-page":"756722","DOI":"10.3389\/fimmu.2021.756722","volume":"12","author":"Q Yang","year":"2021","unstructured":"Yang Q, et al. Single-Cell RNA sequencing reveals the heterogeneity of Tumor-Associated macrophage in Non-Small cell lung cancer and differences between sexes. Front Immunol. 2021;12:756722. https:\/\/doi.org\/10.3389\/fimmu.2021.756722.","journal-title":"Front Immunol"},{"key":"2497_CR52","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.jhep.2023.01.011","volume":"78","author":"Y Liu","year":"2023","unstructured":"Liu Y, et al. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy. J Hepatol. 2023;78:770\u201382. https:\/\/doi.org\/10.1016\/j.jhep.2023.01.011.","journal-title":"J Hepatol"},{"key":"2497_CR53","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.ccell.2023.05.004","volume":"41","author":"S Haston","year":"2023","unstructured":"Haston S, et al. Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer. Cancer Cell. 2023;41:1242\u201360. https:\/\/doi.org\/10.1016\/j.ccell.2023.05.004.","journal-title":"Cancer Cell"},{"key":"2497_CR54","doi-asserted-by":"publisher","first-page":"101078","DOI":"10.1016\/j.xcrm.2023.101078","volume":"4","author":"W Luo","year":"2023","unstructured":"Luo W, et al. Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers. Cell Rep Med. 2023;4:101078. https:\/\/doi.org\/10.1016\/j.xcrm.2023.101078.","journal-title":"Cell Rep Med"},{"key":"2497_CR55","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/s41419-024-07074-x","volume":"15","author":"D Zhang","year":"2024","unstructured":"Zhang D, et al. Novel FABP4\u2009+\u2009C1q\u2009+\u2009macrophages enhance antitumor immunity and associated with response to neoadjuvant pembrolizumab and chemotherapy in NSCLC via AMPK\/JAK\/STAT axis. Cell Death Dis. 2024;15:713\u20137. https:\/\/doi.org\/10.1038\/s41419-024-07074-x.","journal-title":"Cell Death Dis"},{"key":"2497_CR56","doi-asserted-by":"publisher","first-page":"e141814","DOI":"10.1172\/jci.insight.141814","volume":"6","author":"Y Xiao","year":"2021","unstructured":"Xiao Y, et al. Fatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages. JCI Insight. 2021;6:e141814. https:\/\/doi.org\/10.1172\/jci.insight.141814.","journal-title":"JCI Insight"},{"key":"2497_CR57","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41413-022-00211-2","volume":"10","author":"D Guo","year":"2022","unstructured":"Guo D, et al. FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis. Bone Res. 2022;10:45. https:\/\/doi.org\/10.1038\/s41413-022-00211-2.","journal-title":"Bone Res"},{"key":"2497_CR58","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nri3600","volume":"14","author":"T Hussell","year":"2014","unstructured":"Hussell T, et al. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol. 2014;14:81\u201393. https:\/\/doi.org\/10.1038\/nri3600.","journal-title":"Nat Rev Immunol"},{"key":"2497_CR59","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1126\/science.ade2292","volume":"381","author":"R Bill","year":"2023","unstructured":"Bill R, et al. CXCL9:SPP1 macrophage Polarity identifies a network of cellular programs that control human cancers. Science. 2023;381:515\u201324. https:\/\/doi.org\/10.1126\/science.ade2292.","journal-title":"Science"},{"key":"2497_CR60","doi-asserted-by":"publisher","unstructured":"Chen K, et al. Identification of a novel subtype of SPP1\u2009+\u2009macrophages expressing SIRP\u03b1: implications for tumor immune evasion and treatment response prediction. Exp Hematol Oncol. 2024;13. https:\/\/doi.org\/10.1186\/s40164-024-00587-3.","DOI":"10.1186\/s40164-024-00587-3"},{"key":"2497_CR61","doi-asserted-by":"publisher","unstructured":"Fan G, et al. Single-cell and Spatial analyses revealed the co-location of cancer stem cells and SPP1\u2009+\u2009macrophage in hypoxic region that determines the poor prognosis in hepatocellular carcinoma. NPJ Precis Oncol. 2024;8. https:\/\/doi.org\/10.1038\/s41698-024-00564-3.","DOI":"10.1038\/s41698-024-00564-3"},{"key":"2497_CR62","doi-asserted-by":"publisher","unstructured":"Su X, et al. Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage Polarity and prognostic indicators. Mol Cancer. 2024;23. https:\/\/doi.org\/10.1186\/s12943-023-01931-7.","DOI":"10.1186\/s12943-023-01931-7"}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-025-02497-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12943-025-02497-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-025-02497-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:58:02Z","timestamp":1764223082000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/s12943-025-02497-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2497"],"URL":"https:\/\/doi.org\/10.1186\/s12943-025-02497-2","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"assertion":[{"value":"16 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study has been reviewed and approved by the Ethics Committee of Xinqiao Hospital of Army (Third) Military Medical University (No. 145-01) and procedures were conducted in accordance with the Declaration of Helsinki. The lung and nodule tissue specimens were collected from surgical resections of deidentified patients at Xinqiao Hospital, Army (Third Military) Medical University.\u00a0Informed consent was obtained from all patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"298"}}