{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:01:15Z","timestamp":1779379275016,"version":"3.53.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"crossref","award":["No. 320.6750.2024-13-50"],"award-info":[{"award-number":["No. 320.6750.2024-13-50"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New Frontier Research Project for Tumor Supportive Treatment","award":["No. cphcf-2023-255"],"award-info":[{"award-number":["No. cphcf-2023-255"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-026-02689-3","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T07:24:24Z","timestamp":1770449064000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RT\u2013ICI therapy induces a distal immunometabolic axis that shapes systemic macrophage polarization and enhances local T cell immunity"],"prefix":"10.1186","volume":"24","author":[{"given":"Yizhi","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"2689_CR1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/S0140-6736(24)00360-X","volume":"404","author":"C Eng","year":"2024","unstructured":"Eng C, et al. Colorectal cancer. Lancet. 2024;404:294\u2013310.","journal-title":"Lancet"},{"key":"2689_CR2","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.ccell.2021.03.004","volume":"39","author":"A Bertocchi","year":"2021","unstructured":"Bertocchi A, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021;39:708\u201324.","journal-title":"Cancer Cell"},{"key":"2689_CR3","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.ccell.2023.04.011","volume":"41","author":"J Li","year":"2023","unstructured":"Li J, et al. Remodeling of the immune and stromal cell compartment by PD-1 Blockade in mismatch repair-deficient colorectal cancer. Cancer Cell. 2023;41:1152\u201369.","journal-title":"Cancer Cell"},{"key":"2689_CR4","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature25492","volume":"554","author":"D Tauriello","year":"2018","unstructured":"Tauriello D, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554:538\u201343.","journal-title":"Nature"},{"key":"2689_CR5","doi-asserted-by":"publisher","first-page":"113433","DOI":"10.1016\/j.ejca.2023.113433","volume":"196","author":"B Saberzadeh-Ardestani","year":"2024","unstructured":"Saberzadeh-Ardestani B, et al. Metastatic site and clinical outcome of patients with deficient mismatch repair metastatic colorectal cancer treated with an immune checkpoint inhibitor in the first-line setting. Eur J Cancer. 2024;196:113433.","journal-title":"Eur J Cancer"},{"key":"2689_CR6","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41571-023-00782-x","volume":"20","author":"L Galluzzi","year":"2023","unstructured":"Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023;20:543\u201357.","journal-title":"Nat Rev Clin Oncol"},{"key":"2689_CR7","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/s41416-025-03088-0","volume":"133","author":"SA Sakai","year":"2025","unstructured":"Sakai SA, et al. Single-cell Spatial analysis with xenium reveals anti-tumour responses of CXCL13\u2009+\u2009T and CXCL9\u2009+\u2009cells after radiotherapy combined with anti-PD-L1 therapy. Br J Cancer. 2025;133:795\u2013808.","journal-title":"Br J Cancer"},{"key":"2689_CR8","doi-asserted-by":"publisher","first-page":"217347","DOI":"10.1016\/j.canlet.2024.217347","volume":"608","author":"HT Lind","year":"2025","unstructured":"Lind HT, et al. MHC class I upregulation contributes to the therapeutic response to radiotherapy in combination with anti-PD-L1\/anti-TGF-beta in squamous cell carcinomas with enhanced CD8 T cell memory-driven response. Cancer Lett. 2025;608:217347.","journal-title":"Cancer Lett"},{"key":"2689_CR9","doi-asserted-by":"publisher","first-page":"1503517","DOI":"10.3389\/fonc.2025.1503517","volume":"15","author":"Y Ding","year":"2025","unstructured":"Ding Y, et al. High and low dose radiotherapy combined with ICIs for MSS colorectal cancer patients with liver metastases: a phase I study (HaRyPOT). Front Oncol. 2025;15:1503517.","journal-title":"Front Oncol"},{"key":"2689_CR10","doi-asserted-by":"crossref","unstructured":"Bian X et al. Lipid metabolism and cancer. J Exp Med 218. 2021.","DOI":"10.1084\/jem.20201606"},{"key":"2689_CR11","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/s41589-022-01017-3","volume":"18","author":"SA Lim","year":"2022","unstructured":"Lim SA, Su W, Chapman NM, Chi H. Lipid metabolism in T cell signaling and function. Nat Chem Biol. 2022;18:470\u201381.","journal-title":"Nat Chem Biol"},{"key":"2689_CR12","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.tcb.2020.09.006","volume":"30","author":"J Yan","year":"2020","unstructured":"Yan J, Horng T. Lipid metabolism in regulation of macrophage functions. Trends Cell Biol. 2020;30:979\u201389.","journal-title":"Trends Cell Biol"},{"key":"2689_CR13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1161\/CIRCULATIONAHA.105.590273","volume":"113","author":"CH Lee","year":"2006","unstructured":"Lee CH, Plutzky J. Liver X receptor activation and high-density lipoprotein biology: a reversal of fortune? Circulation. 2006;113:5\u20138.","journal-title":"Circulation"},{"key":"2689_CR14","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/s41586-024-08247-6","volume":"637","author":"S Das","year":"2025","unstructured":"Das S, et al. Liver X receptor unlinks intestinal regeneration and tumorigenesis. Nature. 2025;637:1198\u2013206.","journal-title":"Nature"},{"key":"2689_CR15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nsmb.2778","volume":"21","author":"X Lou","year":"2014","unstructured":"Lou X, et al. Structure of the retinoid X receptor alpha-liver X receptor beta (RXRalpha-LXRbeta) heterodimer on DNA. Nat Struct Mol Biol. 2014;21:277\u201381.","journal-title":"Nat Struct Mol Biol"},{"key":"2689_CR16","doi-asserted-by":"publisher","first-page":"24767","DOI":"10.1074\/jbc.M100912200","volume":"276","author":"Y Luo","year":"2001","unstructured":"Luo Y, Liang CP, Tall AR. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J Biol Chem. 2001;276:24767\u201373.","journal-title":"J Biol Chem"},{"key":"2689_CR17","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1189\/jlb.3RU0215-074R","volume":"98","author":"L Sanjurjo","year":"2015","unstructured":"Sanjurjo L, Aran G, Roher N, Valledor AF, Sarrias MR. AIM\/CD5L: a key protein in the control of immune homeostasis and inflammatory disease. J Leukoc Biol. 2015;98:173\u201384.","journal-title":"J Leukoc Biol"},{"key":"2689_CR18","doi-asserted-by":"publisher","first-page":"365","DOI":"10.5603\/FHC.2011.0052","volume":"49","author":"K Kowal","year":"2011","unstructured":"Kowal K, et al. CD163 and its role in inflammation. Folia Histochem Cytobiol. 2011;49:365\u201374.","journal-title":"Folia Histochem Cytobiol"},{"key":"2689_CR19","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.ccell.2021.05.006","volume":"39","author":"A Chow","year":"2021","unstructured":"Chow A, et al. Tim-4(+) cavity-resident macrophages impair anti-tumor CD8(+) T cell immunity. Cancer Cell. 2021;39:973\u201388.","journal-title":"Cancer Cell"},{"key":"2689_CR20","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s13046-023-02900-0","volume":"42","author":"Z Zhang","year":"2023","unstructured":"Zhang Z, et al. Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1. J Exp Clin Cancer Res. 2023;42:316.","journal-title":"J Exp Clin Cancer Res"},{"key":"2689_CR21","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.7150\/thno.89174","volume":"14","author":"L Huang","year":"2024","unstructured":"Huang L, et al. Mrc1(+) macrophage-derived IGF1 mitigates crystal nephropathy by promoting renal tubule cell proliferation via the AKT\/Rb signaling pathway. Theranostics. 2024;14:1764\u201380.","journal-title":"Theranostics"},{"key":"2689_CR22","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao Y, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42:293\u2013304.","journal-title":"Nat Biotechnol"},{"key":"2689_CR23","doi-asserted-by":"publisher","first-page":"W556","DOI":"10.1093\/nar\/gkz430","volume":"47","author":"Z Tang","year":"2019","unstructured":"Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556\u201360.","journal-title":"Nucleic Acids Res"},{"key":"2689_CR24","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, et al. Fast, sensitive and accurate integration of single-cell data with harmony. Nat Methods. 2019;16:1289\u201396.","journal-title":"Nat Methods"},{"key":"2689_CR25","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel AP, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396\u2013401.","journal-title":"Science"},{"key":"2689_CR26","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao J, et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature. 2019;566:496\u2013502.","journal-title":"Nature"},{"key":"2689_CR27","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14:1083\u20136.","journal-title":"Nat Methods"},{"key":"2689_CR28","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","volume":"20","author":"S Jin","year":"2025","unstructured":"Jin S, Plikus MV, Nie Q. CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics. Nat Protoc. 2025;20:180\u2013219.","journal-title":"Nat Protoc"},{"key":"2689_CR29","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","volume":"17","author":"R Browaeys","year":"2020","unstructured":"Browaeys R, Saelens W, Saeys Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2020;17:159\u201362.","journal-title":"Nat Methods"},{"key":"2689_CR30","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41587-021-00830-w","volume":"40","author":"DM Cable","year":"2022","unstructured":"Cable DM, et al. Robust decomposition of cell type mixtures in Spatial transcriptomics. Nat Biotechnol. 2022;40:517\u201326.","journal-title":"Nat Biotechnol"},{"key":"2689_CR31","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41568-020-0246-1","volume":"20","author":"M McLaughlin","year":"2020","unstructured":"McLaughlin M, et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy. Nat Rev Cancer. 2020;20:203\u201317.","journal-title":"Nat Rev Cancer"},{"key":"2689_CR32","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.clinbiochem.2017.07.003","volume":"50","author":"OZ Ismail","year":"2017","unstructured":"Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem. 2017;50:1275\u201380.","journal-title":"Clin Biochem"},{"key":"2689_CR33","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41392-022-01264-9","volume":"8","author":"C Liu","year":"2023","unstructured":"Liu C, et al. Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer. Signal Transduct Target Ther. 2023;8:44.","journal-title":"Signal Transduct Target Ther"},{"key":"2689_CR34","doi-asserted-by":"crossref","unstructured":"Nielsen MC et al. Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells. 9. 2020.","DOI":"10.3390\/cells9051175"},{"key":"2689_CR35","doi-asserted-by":"publisher","first-page":"5275","DOI":"10.7150\/ijbs.86701","volume":"19","author":"CY Ko","year":"2023","unstructured":"Ko CY, et al. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. Int J Biol Sci. 2023;19:5275\u201389.","journal-title":"Int J Biol Sci"},{"key":"2689_CR36","doi-asserted-by":"publisher","first-page":"100686","DOI":"10.1016\/j.jlr.2024.100686","volume":"65","author":"S Sarkar","year":"2024","unstructured":"Sarkar S, et al. APOA2 increases cholesterol efflux capacity to plasma HDL by displacing the C-terminus of resident APOA1. J Lipid Res. 2024;65:100686.","journal-title":"J Lipid Res"},{"key":"2689_CR37","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41586-021-03442-1","volume":"593","author":"BI Reinfeld","year":"2021","unstructured":"Reinfeld BI, et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 2021;593:282\u20138.","journal-title":"Nature"},{"key":"2689_CR38","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1042\/BST20150112","volume":"43","author":"KE Waddington","year":"2015","unstructured":"Waddington KE, Jury EC. Pineda-Torra, I. Liver X receptors in immune cell function in humans. Biochem Soc Trans. 2015;43:752\u20137.","journal-title":"Biochem Soc Trans"},{"key":"2689_CR39","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.tem.2020.01.003","volume":"31","author":"LL Blauw","year":"2020","unstructured":"Blauw LL, Wang Y, Willems VDK, Rensen P. A novel role for CETP as immunological gatekeeper: Raising HDL to cure sepsis? Trends Endocrinol Metab. 2020;31:334\u201343.","journal-title":"Trends Endocrinol Metab"},{"key":"2689_CR40","doi-asserted-by":"crossref","unstructured":"Zeljkovic A et al. Revealing the role of High-Density lipoprotein in colorectal cancer. Int J Mol Sci 22. 2021.","DOI":"10.3390\/ijms22073352"},{"key":"2689_CR41","doi-asserted-by":"publisher","first-page":"480","DOI":"10.3389\/fimmu.2018.00480","volume":"9","author":"L Sanjurjo","year":"2018","unstructured":"Sanjurjo L, et al. CD5L promotes M2 macrophage polarization through Autophagy-Mediated upregulation of ID3. Front Immunol. 2018;9:480.","journal-title":"Front Immunol"},{"key":"2689_CR42","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/nature21356","volume":"543","author":"Turner K. M.","year":"2017","unstructured":"K. M. Turner. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 2017;543:122\u20135.","journal-title":"Nature"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-02689-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02689-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02689-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T09:13:00Z","timestamp":1772701980000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-02689-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,7]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2689"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-02689-3","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,7]]},"assertion":[{"value":"14 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2026","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 research was approved by the Research Ethics Committee of Jiangsu Cancer Hospital [No.2023-046]. All patients have written informed consent for participation in this study.","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":"159"}}