{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:02:25Z","timestamp":1790294545703,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":83,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"DOI":"10.1007\/s00262-026-04427-7","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:45:25Z","timestamp":1783136725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative single-cell and multi-omics analysis of ZBTB21-mediated serine metabolism in colorectal cancer: from metabolic reprogramming to immune microenvironment modulation"],"prefix":"10.1007","volume":"75","author":[{"given":"Yimei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijia","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopin","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"issue":"3","key":"4427_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229\u2013263","journal-title":"CA Cancer J Clin"},{"issue":"2","key":"4427_CR2","first-page":"89","volume":"14","author":"P Rawla","year":"2019","unstructured":"Rawla P, Sunkara T, Barsouk A (2019) Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Przeglad gastroenterologiczny 14(2):89\u2013103","journal-title":"Przeglad gastroenterologiczny"},{"issue":"17","key":"4427_CR3","doi-asserted-by":"publisher","first-page":"e71185","DOI":"10.1002\/cam4.71185","volume":"14","author":"R Zhou","year":"2025","unstructured":"Zhou R, Wang F, Wen J, Zhou X, Wen Y (2025) Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches. Cancer Med 14(17):e71185","journal-title":"Cancer Med"},{"key":"4427_CR4","doi-asserted-by":"publisher","first-page":"102156","DOI":"10.1016\/j.tranon.2024.102156","volume":"50","author":"R Qin","year":"2024","unstructured":"Qin R, Fan X, Huang Y, Chen S, Ding R, Yao Y et al (2024) Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance. Translational oncology 50:102156","journal-title":"Translational oncology"},{"key":"4427_CR5","doi-asserted-by":"publisher","first-page":"1353787","DOI":"10.3389\/fimmu.2024.1353787","volume":"15","author":"A Nicolini","year":"2024","unstructured":"Nicolini A, Ferrari P (2024) Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression, immune escape, and response to immunotherapy. Front Immunol 15:1353787","journal-title":"Front Immunol"},{"issue":"1","key":"4427_CR6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12964-024-02016-8","volume":"23","author":"Z Chen","year":"2025","unstructured":"Chen Z, Xu J, Fang K, Jiang H, Leng Z, Wu H et al (2025) FOXC1-mediated serine metabolism reprogramming enhances colorectal cancer growth and 5-FU resistance under serine restriction. Cell Commun Signal 23(1):13","journal-title":"Cell Commun Signal"},{"issue":"2","key":"4427_CR7","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.molcel.2015.12.014","volume":"61","author":"OD Maddocks","year":"2016","unstructured":"Maddocks OD, Labuschagne CF, Adams PD, Vousden KH (2016) Serine Metabolism Supports the Methionine Cycle and DNA\/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. Mol Cell 61(2):210\u2013221","journal-title":"Mol Cell"},{"issue":"1","key":"4427_CR8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s13046-025-03498-1","volume":"44","author":"Y Li","year":"2025","unstructured":"Li Y, Peng J, Wu D, Xie Q, Hou Y, Li L et al (2025) Histone lactylation-boosted AURKB facilitates colorectal cancer progression by inhibiting HNRNPM-mediated PSAT1 mRNA degradation. Journal of experimental & clinical cancer research\u202f: CR 44(1):233","journal-title":"Journal of experimental & clinical cancer research : CR"},{"issue":"10","key":"4427_CR9","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1038\/s41401-022-00894-7","volume":"43","author":"S Li","year":"2022","unstructured":"Li S, Yang H, Li W, Liu JY, Ren LW, Yang YH et al (2022) ADH1C inhibits progression of colorectal cancer through the ADH1C\/PHGDH \/PSAT1\/serine metabolic pathway. Acta Pharmacol Sin 43(10):2709\u20132722","journal-title":"Acta Pharmacol Sin"},{"issue":"13","key":"4427_CR10","doi-asserted-by":"publisher","first-page":"4175","DOI":"10.7150\/jca.94630","volume":"15","author":"Y Jia","year":"2024","unstructured":"Jia Y, Feng G, Chen S, Li W, Jia Z, Wang J et al (2024) Metabolic Heterogeneity of Tumor Cells and its Impact on Colon Cancer Metastasis: Insights from Single-Cell and Bulk Transcriptome Analyses. J Cancer 15(13):4175\u20134196","journal-title":"J Cancer"},{"issue":"1","key":"4427_CR11","doi-asserted-by":"publisher","first-page":"1726556","DOI":"10.1080\/2162402X.2020.1726556","volume":"9","author":"Z Xiao","year":"2020","unstructured":"Xiao Z, Locasale JW, Dai Z (2020) Metabolism in the tumor microenvironment: insights from single-cell analysis. Oncoimmunology 9(1):1726556","journal-title":"Oncoimmunology"},{"issue":"10","key":"4427_CR12","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1007\/s12032-025-03007-6","volume":"42","author":"Y Du","year":"2025","unstructured":"Du Y, Miao Z, Li P, Feng D, Liu M, Ji A et al (2025) Machine learning integration of bulk and single-cell RNA-seq data reveals glycolytic heterogeneity in colorectal cancer. Medical oncology (Northwood, London, England) 42(10):458","journal-title":"Medical oncology (Northwood, London, England)"},{"issue":"13","key":"4427_CR13","doi-asserted-by":"publisher","first-page":"e70721","DOI":"10.1111\/jcmm.70721","volume":"29","author":"A Li","year":"2025","unstructured":"Li A, Wu Q, Xu Y, Gu Y, Wang X, Liu J et al (2025) Multi-omics analysis and real-world data validation of serine metabolism-related genes in colorectal cancer. J Cell Mol Med 29(13):e70721","journal-title":"J Cell Mol Med"},{"key":"4427_CR14","doi-asserted-by":"publisher","first-page":"768861","DOI":"10.3389\/fphar.2021.768861","volume":"12","author":"KW Hon","year":"2021","unstructured":"Hon KW, Zainal Abidin SA, Othman I, Naidu R (2021) The crosstalk between signaling pathways and cancer metabolism in colorectal cancer. Front Pharmacol 12:768861","journal-title":"Front Pharmacol"},{"key":"4427_CR15","doi-asserted-by":"publisher","first-page":"1575829","DOI":"10.3389\/fimmu.2025.1575829","volume":"16","author":"T Sun","year":"2025","unstructured":"Sun T, Chen Y, Chen YX (2025) Single-cell and bulk transcriptome analyses reveal elevated amino acid metabolism promoting tumor-directed immune evasion in colorectal cancer. Front Immunol 16:1575829","journal-title":"Front Immunol"},{"issue":"5","key":"4427_CR16","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.advnut.2023.05.007","volume":"14","author":"W Shunxi","year":"2023","unstructured":"Shunxi W, Xiaoxue Y, Guanbin S, Li Y, Junyu J, Wanqian L (2023) Serine metabolic reprogramming in tumorigenesis, tumor immunity, and clinical treatment. Adv Nutr 14(5):1050\u20131066","journal-title":"Adv Nutr"},{"key":"4427_CR17","first-page":"102157","volume":"43","author":"C Zhang","year":"2025","unstructured":"Zhang C, Rao Z, Zhan X, Qin J, Yang L, Yin Q et al (2025) Deciphering tryptophan metabolism in colorectal cancer through multi-omics analysis. Biochem Biophys Rep 43:102157","journal-title":"Biochem Biophys Rep"},{"issue":"1","key":"4427_CR18","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s12967-025-06351-3","volume":"23","author":"Y Jiang","year":"2025","unstructured":"Jiang Y, Long G, Huang X, Wang W, Cheng B, Pan W (2025) Single-cell transcriptomic analysis reveals dynamic changes in the liver microenvironment during colorectal cancer metastatic progression. J Transl Med 23(1):336","journal-title":"J Transl Med"},{"key":"4427_CR19","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3389\/fgene.2013.00270","volume":"4","author":"P Waldmann","year":"2013","unstructured":"Waldmann P, M\u00e9sz\u00e1ros G, Gredler B, Fuerst C, S\u00f6lkner J (2013) Evaluation of the lasso and the elastic net in genome-wide association studies. Front Genet 4:270","journal-title":"Front Genet"},{"issue":"1","key":"4427_CR20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1080\/10888438.2015.1107073","volume":"20","author":"K Matsuki","year":"2016","unstructured":"Matsuki K, Kuperman V, Van Dyke JA (2016) The Random Forests statistical technique: an examination of its value for the study of reading. Sci Stud Read 20(1):20\u201333","journal-title":"Sci Stud Read"},{"issue":"1","key":"4427_CR21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1089\/neur.2020.0009","volume":"1","author":"T Inoue","year":"2020","unstructured":"Inoue T, Ichikawa D, Ueno T, Cheong M, Inoue T, Whetstone WD et al (2020) XGBoost, a Machine Learning Method, Predicts Neurological Recovery in Patients with Cervical Spinal Cord Injury. Neurotrauma reports 1(1):8\u201316","journal-title":"Neurotrauma reports"},{"issue":"1","key":"4427_CR22","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/s12859-018-2451-4","volume":"19","author":"H Sanz","year":"2018","unstructured":"Sanz H, Valim C, Vegas E, Oller JM, Reverter F (2018) SVM-RFE: selection and visualization of the most relevant features through non-linear kernels. BMC Bioinformatics 19(1):432","journal-title":"BMC Bioinformatics"},{"issue":"R1","key":"4427_CR23","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","volume":"23","author":"G Davey Smith","year":"2014","unstructured":"Davey Smith G, Hemani G (2014) Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 23(R1):R89-98","journal-title":"Hum Mol Genet"},{"issue":"1","key":"4427_CR24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12967-025-06103-3","volume":"23","author":"Y Wang","year":"2025","unstructured":"Wang Y, Qiu X, Li Q, Qin J, Ye L, Zhang X et al (2025) Single-cell and spatial-resolved profiling reveals cancer-associated fibroblast heterogeneity in colorectal cancer metabolic subtypes. J Transl Med 23(1):175","journal-title":"J Transl Med"},{"issue":"1","key":"4427_CR25","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41420-024-01865-z","volume":"10","author":"X Chen","year":"2024","unstructured":"Chen X, Ma Z, Yi Z, Wu E, Shang Z, Tuo B et al (2024) The effects of metabolism on the immune microenvironment in colorectal cancer. Cell Death Discov 10(1):118","journal-title":"Cell Death Discov"},{"issue":"5","key":"4427_CR26","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41419-024-06598-6","volume":"15","author":"J Xiao","year":"2024","unstructured":"Xiao J, Yu X, Meng F, Zhang Y, Zhou W, Ren Y et al (2024) Integrating spatial and single-cell transcriptomics reveals tumor heterogeneity and intercellular networks in colorectal cancer. Cell Death Dis 15(5):326","journal-title":"Cell Death Dis"},{"issue":"1","key":"4427_CR27","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/s41698-025-01005-5","volume":"9","author":"Y Sun","year":"2025","unstructured":"Sun Y, Zhang M, Zhao Y, Yan Y, Wang L, Liu X et al (2025) Spatial transcriptomics reveals macrophage domestication by epithelial cells promotes immunotherapy resistance in small cell lung cancer. NPJ precision oncology 9(1):252","journal-title":"NPJ precision oncology"},{"issue":"14","key":"4427_CR28","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1111\/1759-7714.15283","volume":"15","author":"L Shen","year":"2024","unstructured":"Shen L, Liu J, Hu F, Fang Y, Wu Y, Zhao W et al (2024) Single-cell RNA sequencing reveals aberrant sphingolipid metabolism in non-small cell lung cancer impacts tumor-associated macrophages and stimulates angiogenesis via macrophage inhibitory factor signaling. Thoracic cancer 15(14):1164\u20131175","journal-title":"Thoracic cancer"},{"issue":"9","key":"4427_CR29","doi-asserted-by":"publisher","first-page":"100262","DOI":"10.1016\/j.mocell.2025.100262","volume":"48","author":"J Zhang","year":"2025","unstructured":"Zhang J, Lee SE, Yoon J, Ku BJ, Park JO, Kang DH et al (2025) Multifaceted role of serine hydroxymethyltransferase in health and disease. Mol Cells 48(9):100262","journal-title":"Mol Cells"},{"issue":"22","key":"4427_CR30","doi-asserted-by":"publisher","first-page":"6321","DOI":"10.1158\/0008-5472.CAN-17-1589","volume":"77","author":"H Yoshino","year":"2017","unstructured":"Yoshino H, Nohata N, Miyamoto K, Yonemori M, Sakaguchi T, Sugita S et al (2017) PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2\u03b1-Targeting Therapy for Renal Cell Carcinoma. Can Res 77(22):6321\u20136329","journal-title":"Can Res"},{"issue":"7","key":"4427_CR31","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1038\/s12276-024-01268-1","volume":"56","author":"CM Lee","year":"2024","unstructured":"Lee CM, Hwang Y, Kim M, Park YC, Kim H, Fang S (2024) PHGDH: a novel therapeutic target in cancer. Exp Mol Med 56(7):1513\u20131522","journal-title":"Exp Mol Med"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-026-04427-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04427-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04427-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:46:56Z","timestamp":1790293616000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-026-04427-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,4]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["4427"],"URL":"https:\/\/doi.org\/10.1007\/s00262-026-04427-7","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,4]]},"assertion":[{"value":"14 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by Ruijin Hospital Ethics Committee, Shanghai JiaoTong University School of Medicine (reference number: 2022\u2013336). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All data published here are under the consent for publication. Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"237"}}