{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:52:53Z","timestamp":1790952773714,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA174798"],"award-info":[{"award-number":["R01CA174798"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["5P50CA140388"],"award-info":[{"award-number":["5P50CA140388"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA276235"],"award-info":[{"award-number":["CA276235"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP230247"],"award-info":[{"award-number":["RP230247"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-21-1-0522"],"award-info":[{"award-number":["W81XWH-21-1-0522"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prostate Cancer Prostatic Dis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer (PCa) bone lesions are bone-forming, which contribute to an immunosuppressive bone-tumor microenvironment (bone-TME). Targeting PCa-induced bone with the radiopharmaceutical Radium-223 (Ra223) is approved for men with bone-metastatic castration-resistant PCa (bmCRPC). We studied the effect of Ra223 on spatial localization of tumor and immune cells in bmCRPC tumor biopsies to gain insights into therapeutic immunomodulation of the bone-TME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transiliac bone marrow biopsies were performed at baseline and end of treatment (EOT) in 24 patients with bmCRPC treated with Ra223. In three patients with paired specimens containing tumor, multiplex immunofluorescence was performed with antibodies for a tumor cell marker (CK), T-cell markers (CD3, CD4, CD8, FOXP3, and granzyme B), macrophage markers (CD68 [total macrophages] and CD206 [M2-like macrophages]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In all three patients, we observed enrichment of CD68\n                      <jats:sup>+<\/jats:sup>\n                      macrophages, around tumor-induced bone at baseline. CD3 staining revealed T cell depletion where tumor cells formed large sheets but not where tumor cells were scattered. The effects of Ra223 on tumor cells and T cell subsets were heterogeneous. In one patient, tumor cells were reduced, and CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were increased. In a second patient who evidenced osteolytic progression, tumor cells were increased while CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were decreased. In a third patient, there was high number of tumor cells at baseline that modestly decreased and the number of CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells modestly increased after Ra223 treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The changes in tumor cell numbers after Ra223 treatment seemed to be inversely correlated with changes in CD3\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      and CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      cells, but not with other immune cells, in these 3 patients. Further characterization of immune cells in the bone-TME will be required before developing strategies to enhance immunotherapy efficacy in bmCRPC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>This study does not report the clinical results of a clinical trial, but it does use samples from a completed clinical trial that is registered with clinicaltrials.gov (NCT02135484).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41391-025-01069-1","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T21:26:34Z","timestamp":1766784394000},"page":"602-610","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatial immune profiling of bone-metastatic castration-resistant prostate cancer reveals radium-223 immunomodulates the bone-tumor microenvironment"],"prefix":"10.1038","volume":"29","author":[{"given":"Paul G.","family":"Corn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Troncoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devaki Shilpa","family":"Surasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaffer A.","family":"Ajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-1711","authenticated-orcid":false,"given":"Christopher J.","family":"Logothetis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-7249","authenticated-orcid":false,"given":"Guocan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-6950","authenticated-orcid":false,"given":"Theocharis","family":"Panaretakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue-Hwa","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"1069_CR1","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/sj.bjc.6605334","volume":"101","author":"C Messiou","year":"2009","unstructured":"Messiou C, Cook G, deSouza NM. Imaging metastatic bone disease from carcinoma of the prostate. Br J Cancer. 2009;101:1225\u201332.","journal-title":"Br J Cancer"},{"key":"1069_CR2","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.clgc.2018.07.009","volume":"16","author":"T Lengana","year":"2018","unstructured":"Lengana T, Lawal IO, Boshomane TG, Popoola GO, Mokoala KMG, Moshokoa E, et al. (68)Ga-PSMA PET\/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli?. Clin Genitourin Cancer. 2018;16:392\u2013401.","journal-title":"Clin Genitourin Cancer"},{"key":"1069_CR3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1053\/j.semnuclmed.2023.07.004","volume":"54","author":"N Mohseninia","year":"2024","unstructured":"Mohseninia N, Zamani-Siahkali N, Harsini S, Divband G, Pirich C, Beheshti M. Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging. Semin Nucl Med. 2024;54:97\u2013118.","journal-title":"Semin Nucl Med"},{"key":"1069_CR4","doi-asserted-by":"publisher","first-page":"5194","DOI":"10.1158\/0008-5472.CAN-10-4374","volume":"71","author":"YC Lee","year":"2011","unstructured":"Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, et al. BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res. 2011;71:5194\u2013203.","journal-title":"Cancer Res"},{"key":"1069_CR5","doi-asserted-by":"publisher","first-page":"7554","DOI":"10.1158\/0008-5472.CAN-05-1317","volume":"65","author":"CL Hall","year":"2005","unstructured":"Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET. Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res. 2005;65:7554\u201360.","journal-title":"Cancer Res"},{"key":"1069_CR6","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1158\/0008-5472.CAN-03-1382","volume":"64","author":"J Dai","year":"2004","unstructured":"Dai J, Kitagawa Y, Zhang J, Yao Z, Mizokami A, Cheng S, et al. Vascular endothelial growth factor contributes to the prostate cancer-induced osteoblast differentiation mediated by bone morphogenetic protein. Cancer Res. 2004;64:994\u20139.","journal-title":"Cancer Res"},{"key":"1069_CR7","doi-asserted-by":"publisher","first-page":"5785","DOI":"10.1158\/0008-5472.CAN-07-6541","volume":"68","author":"J Dai","year":"2008","unstructured":"Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, Keller ET. Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res. 2008;68:5785\u201394.","journal-title":"Cancer Res"},{"key":"1069_CR8","doi-asserted-by":"publisher","first-page":"8274","DOI":"10.1158\/0008-5472.CAN-05-1891","volume":"65","author":"J Dai","year":"2005","unstructured":"Dai J, Keller J, Zhang J, Lu Y, Yao Z, Keller ET. Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res. 2005;65:8274\u201385.","journal-title":"Cancer Res"},{"key":"1069_CR9","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41388-021-02131-7","volume":"41","author":"YC Lee","year":"2022","unstructured":"Lee YC, Lin SC, Yu G, Zhu M, Song JH, Rivera K, et al. Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP\/TAZ inhibition. Oncogene. 2022;41:757\u201369.","journal-title":"Oncogene"},{"key":"1069_CR10","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.devcel.2017.05.005","volume":"41","author":"SC Lin","year":"2017","unstructured":"Lin SC, Lee YC, Yu G, Cheng CJ, Zhou X, Chu K, et al. Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. Dev cell. 2017;41:467\u2013480 e463.","journal-title":"Dev cell"},{"key":"1069_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102388","volume":"24","author":"G Yu","year":"2021","unstructured":"Yu G, Shen P, Lee YC, Pan J, Song JH, Pan T, et al. Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4. iScience. 2021;24:102388.","journal-title":"iScience"},{"key":"1069_CR12","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1056\/NEJMoa1213755","volume":"369","author":"C Parker","year":"2013","unstructured":"Parker C, Nilsson S, Heinrich D, Helle SI, O\u2019Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213\u201323.","journal-title":"N Engl J Med"},{"key":"1069_CR13","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1093\/annonc\/mdx044","volume":"28","author":"O Sartor","year":"2017","unstructured":"Sartor O, Coleman RE, Nilsson S, Heinrich D, Helle SI, O\u2019Sullivan JM, et al. An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. Ann Oncol. 2017;28:1090\u20137.","journal-title":"Ann Oncol"},{"key":"1069_CR14","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.cell.2019.10.029","volume":"179","author":"S Jiao","year":"2019","unstructured":"Jiao S, Subudhi SK, Aparicio A, Ge Z, Guan B, Miura Y, et al. Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy. Cell. 2019;179:1177\u20131190 e1113.","journal-title":"Cell"},{"key":"1069_CR15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2402903121","volume":"121","author":"G Yu","year":"2024","unstructured":"Yu G, Corn PG, Mak CSL, Liang X, Zhang M, Troncoso P, et al. Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization. Proc Natl Acad Sci USA. 2024;121:e2402903121.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1069_CR16","doi-asserted-by":"publisher","first-page":"9209","DOI":"10.1158\/0008-5472.CAN-04-2442","volume":"64","author":"RB Shah","year":"2004","unstructured":"Shah RB, Mehra R, Chinnaiyan AM, Shen R, Ghosh D, Zhou M, et al. Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res. 2004;64:9209\u201316.","journal-title":"Cancer Res"},{"key":"1069_CR17","doi-asserted-by":"publisher","first-page":"E4762","DOI":"10.1073\/pnas.1319948110","volume":"110","author":"JM Drake","year":"2013","unstructured":"Drake JM, Graham NA, Lee JK, Stoyanova T, Faltermeier CM, Sud S, et al. Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets. Proc Natl Acad Sci USA. 2013;110:E4762\u20134769.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1069_CR18","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1158\/1078-0432.CCR-20-4790","volume":"27","author":"I Vardaki","year":"2021","unstructured":"Vardaki I, Corn P, Gentile E, Song JH, Madan N, Hoang A, et al. Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles from the Metastatic Prostate Cancer Bone Microenvironment. Clin Cancer Res. 2021;27:3253\u201364.","journal-title":"Clin Cancer Res"},{"key":"1069_CR19","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1200\/JCO.2015.64.2702","volume":"34","author":"HI Scher","year":"2016","unstructured":"Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402\u201318.","journal-title":"J Clin Oncol"},{"key":"1069_CR20","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1053\/j.semnuclmed.2016.07.003","volume":"46","author":"W Langsteger","year":"2016","unstructured":"Langsteger W, Rezaee A, Pirich C, Beheshti M. 18)F-NaF-PET\/CT and (99m)Tc-MDP Bone Scintigraphy in the Detection of Bone Metastases in Prostate Cancer. Semin Nucl Med. 2016;46:491\u2013501.","journal-title":"Semin Nucl Med"},{"key":"1069_CR21","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1056\/NEJMoa1503747","volume":"373","author":"CJ Sweeney","year":"2015","unstructured":"Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373:737\u201346.","journal-title":"N Engl J Med"},{"key":"1069_CR22","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1126\/science.aaa6204","volume":"348","author":"JA Joyce","year":"2015","unstructured":"Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348:74\u201380.","journal-title":"Science"},{"key":"1069_CR23","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1158\/0008-5472.CAN-24-2223","volume":"85","author":"H Chi","year":"2025","unstructured":"Chi H, Deng S, Xu K, Zhang Y, Song T, Yu J, et al. SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint That Enables Tumor Immune Evasion by Impairing T-cell Cytotoxicity. Cancer Res. 2025;85:912\u201324.","journal-title":"Cancer Res"},{"key":"1069_CR24","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41577-019-0127-6","volume":"19","author":"DG DeNardo","year":"2019","unstructured":"DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol. 2019;19:369\u201382.","journal-title":"Nat Rev Immunol"},{"key":"1069_CR25","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1158\/2159-8290.CD-24-0100","volume":"14","author":"KL Donahue","year":"2024","unstructured":"Donahue KL, Watkoske HR, Kadiyala P, Du W, Brown K, Scales MK, et al. Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth. Cancer Discov. 2024;14:1964\u201389.","journal-title":"Cancer Discov"},{"key":"1069_CR26","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1158\/1078-0432.CCR-19-2389","volume":"26","author":"PG Corn","year":"2020","unstructured":"Corn PG, Zhang M, Nogueras-Gonzalez GM, Xiao L, Zurita AJ, Subudhi SK, et al. A Phase II Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naive Metastatic Prostate Cancer. Clin Cancer Res. 2020;26:990\u20139.","journal-title":"Clin Cancer Res"},{"key":"1069_CR27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.eururo.2014.05.005","volume":"67","author":"E Efstathiou","year":"2015","unstructured":"Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015;67:53\u201360.","journal-title":"Eur Urol"},{"key":"1069_CR28","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1148\/radiol.13121782","volume":"269","author":"CE Spritzer","year":"2013","unstructured":"Spritzer CE, Afonso PD, Vinson EN, Turnbull JD, Morris KK, Foye A, et al. Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration-resistant prostate cancer-factors affecting diagnostic success. Radiology. 2013;269:816\u201323.","journal-title":"Radiology"},{"key":"1069_CR29","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/j.ccell.2021.09.005","volume":"39","author":"Y Kfoury","year":"2021","unstructured":"Kfoury Y, Baryawno N, Severe N, Mei S, Gustafsson K, Hirz T, et al. Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment. Cancer Cell. 2021;39:1464\u20131478 e1468.","journal-title":"Cancer Cell"},{"key":"1069_CR30","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/BF01623379","volume":"3","author":"DW Dempster","year":"1993","unstructured":"Dempster DW, Ferguson-Pell MW, Mellish RW, Cochran GV, Xie F, Fey C, et al. Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine. Osteoporos Int. 1993;3:90\u201396.","journal-title":"Osteoporos Int"},{"key":"1069_CR31","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1159\/000489672","volume":"47","author":"SM Ott","year":"2018","unstructured":"Ott SM. Cortical or Trabecular Bone: What\u2019s the Difference?. Am J Nephrol. 2018;47:373\u20135.","journal-title":"Am J Nephrol"}],"container-title":["Prostate Cancer and Prostatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01069-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01069-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01069-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T21:44:50Z","timestamp":1786657490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01069-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1069"],"URL":"https:\/\/doi.org\/10.1038\/s41391-025-01069-1","relation":{},"ISSN":["1365-7852","1476-5608"],"issn-type":[{"value":"1365-7852","type":"print"},{"value":"1476-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]},"assertion":[{"value":"4 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no potential competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Informed consent was obtained from each patient for the studies described above and subsequent publication.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This study was approved by the University of Texas MD Anderson Cancer Center Institutional Review Board and Informed consent was obtained from each patient. All methods were performed in accordance with the relevant guidelines and regulations.","order":3,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Ethics"}}]}}