{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:59:55Z","timestamp":1791644395656,"version":"4.3.4"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Chinese Institutes for Medical Research (CIMR) foundation and Capital Medical University Startup fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"DOI":"10.1186\/s13014-026-02810-3","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:45:16Z","timestamp":1772628316000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Local FLASH radiation exhibits a double-edged effect on the mouse immune system"],"prefix":"10.1186","volume":"21","author":[{"given":"Xiaohang","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimeng","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinuo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuimeng","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Ming","family":"Spring Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Yue","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"2810_CR1","doi-asserted-by":"publisher","first-page":"1490129","DOI":"10.3389\/fimmu.2024.1490129","volume":"15","author":"D Zhang","year":"2024","unstructured":"Zhang D, Zhao J, Zhang Y, Jiang H, Liu D. Revisiting immune checkpoint inhibitors: new strategies to enhance efficacy and reduce toxicity. Front Immunol. 2024;15:1490129.","journal-title":"Front Immunol"},{"issue":"2","key":"2810_CR2","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","volume":"4","author":"R Barroso-Sousa","year":"2018","unstructured":"Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):173\u201382.","journal-title":"JAMA Oncol"},{"key":"2810_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.radonc.2022.10.019","volume":"177","author":"B Venkatesulu","year":"2022","unstructured":"Venkatesulu B, Giridhar P, Pujari L, Chou B, Lee JH, Block AM, Upadhyay R, Welsh JS, Harkenrider MM, Krishnan S, Verma V, En Hsieh C, Pradhan S, Small W Jr, Solanki AA. Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy. Radiother Oncol. 2022;177:81\u201394.","journal-title":"Radiother Oncol"},{"key":"2810_CR4","doi-asserted-by":"publisher","first-page":"217347","DOI":"10.1016\/j.canlet.2024.217347","volume":"608","author":"HT Lind","year":"2025","unstructured":"Lind HT, Hall SC, Strait AA, Goon JB, Aleman JD, Chen SMY, Karam SD, Young CD, Wang JH, Wang XJ. MHC class I upregulation contributes to the therapeutic response to radiotherapy in combination with anti-PD-L1\/anti-TGF-\u03b2 in squamous cell carcinomas with enhanced CD8 T cell memory-driven response. Cancer Lett. 2025;608:217347.","journal-title":"Cancer Lett"},{"issue":"12","key":"2810_CR5","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1158\/1078-0432.CCR-19-2034","volume":"26","author":"A Arina","year":"2020","unstructured":"Arina A, Gutiontov SI, Weichselbaum RR. Radiotherapy and Immunotherapy for Cancer: From Systemic to Multisite. Clin Cancer Res. 2020;26(12):2777\u201382.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"2810_CR6","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.ijrobp.2021.07.1695","volume":"111","author":"PJJ Damen","year":"2021","unstructured":"Damen PJJ, Kroese TE, van Hillegersberg R, Schuit E, Peters M, Verhoeff JJC, Lin SH, van Rossum PSN. The Influence of Severe Radiation-Induced Lymphopenia on Overall Survival in Solid Tumors: A Systematic Review and Meta-Analysis. Int J Radiat Oncol Biol Phys. 2021;111(4):936\u201348.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2810_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.radonc.2021.12.038","volume":"167","author":"S Monti","year":"2022","unstructured":"Monti S, Xu T, Liao Z, Mohan R, Cella L, Palma G. On the interplay between dosiomics and genomics in radiation-induced lymphopenia of lung cancer patients. Radiother Oncol. 2022;167:219\u201325.","journal-title":"Radiother Oncol"},{"issue":"1","key":"2810_CR8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13046-023-02621-4","volume":"42","author":"TN Pham","year":"2023","unstructured":"Pham TN, Coupey J, Candeias SM, Ivanova V, Valable S, Thariat J. Beyond lymphopenia, unraveling radiation-induced leucocyte subpopulation kinetics and mechanisms through modeling approaches. J Exp Clin Cancer Res. 2023;42(1):50.","journal-title":"J Exp Clin Cancer Res"},{"issue":"24","key":"2810_CR9","doi-asserted-by":"publisher","first-page":"6193","DOI":"10.3390\/cancers13246193","volume":"13","author":"JY Jin","year":"2021","unstructured":"Jin JY, Hu C, Xiao Y, Zhang H, Paulus R, Ellsworth SG, Schild SE, Bogart JA, Dobelbower MC, Kavadi VS, Narayan S, Iyengar P, Robinson C, Greenberger JS, Koprowski C, Machtay M, Curran W, Choy H, Bradley JD, Kong FS. Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617. Cancers (Basel). 2021;13(24):6193.","journal-title":"Cancers (Basel)"},{"key":"2810_CR10","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.radonc.2020.04.054","volume":"149","author":"JY Jin","year":"2020","unstructured":"Jin JY, Gu A, Wang W, Oleinick NL, Machtay M, Spring Kong FM. Ultra-high dose rate effect on circulating immune cells: A potential mechanism for FLASH effect? Radiother Oncol. 2020;149:55\u201362.","journal-title":"Radiother Oncol"},{"key":"2810_CR11","doi-asserted-by":"publisher","first-page":"110041","DOI":"10.1016\/j.radonc.2023.110041","volume":"190","author":"L Cella","year":"2024","unstructured":"Cella L, Monti S, Pacelli R, Palma G. Modeling frameworks for radiation induced lymphopenia: A critical review. Radiother Oncol. 2024;190:110041.","journal-title":"Radiother Oncol"},{"key":"2810_CR12","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.critrevonc.2018.01.003","volume":"123","author":"BP Venkatesulu","year":"2018","unstructured":"Venkatesulu BP, Mallick S, Lin SH, Krishnan S. A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors. Crit Rev Oncol Hematol. 2018;123:42\u201351.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"1","key":"2810_CR13","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s13014-021-01969-1","volume":"16","author":"AV Reddy","year":"2021","unstructured":"Reddy AV, Deek MP, Jackson JF, Hill CS, Sehgal S, He J, Zheng L, Herman JM, Meyer J, Narang AK. Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy. Radiat Oncol. 2021;16(1):242.","journal-title":"Radiat Oncol"},{"issue":"3","key":"2810_CR14","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1182\/blood-2009-02-206870","volume":"114","author":"Y Lee","year":"2009","unstructured":"Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8\u2009+\u2009T cells: changing strategies for cancer treatment. Blood. 2009;114(3):589\u201395.","journal-title":"Blood"},{"issue":"1","key":"2810_CR15","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/1097-0142(197007)26:1<232::AID-CNCR2820260129>3.0.CO;2-D","volume":"26","author":"HD Suit","year":"1970","unstructured":"Suit HD, Kastelan A. Immunologic status of host and response of a methylcholanthrene-induced sarcoma to local x-irradiation. Cancer. 1970;26(1):232\u20138.","journal-title":"Cancer"},{"issue":"4","key":"2810_CR16","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bjc.1953.46","volume":"7","author":"A COHEN","year":"1953","unstructured":"COHEN A. Radiobiology of the C3H mouse mammary carcinoma: the effect of body dose on the radiocurability of the tumour treated in situ. Br J Cancer. 1953;7(4):452\u20135.","journal-title":"Br J Cancer"},{"key":"2810_CR17","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.radonc.2020.02.015","volume":"146","author":"C Xu","year":"2020","unstructured":"Xu C, Jin JY, Zhang M, Liu A, Wang J, Mohan R, Kong FS, Lin SH. The impact of the effective dose to immune cells on lymphopenia and survival of esophageal cancer after chemoradiotherapy. Radiother Oncol. 2020;146:180\u20136.","journal-title":"Radiother Oncol"},{"key":"2810_CR18","doi-asserted-by":"publisher","first-page":"768956","DOI":"10.3389\/fonc.2022.768956","volume":"12","author":"F Chen","year":"2022","unstructured":"Chen F, Jin JY, Hui TSK, Jing H, Zhang H, Nong Y, Han Y, Wang W, Ma L, Yi F, Chen Q, Zhang Y, Fu P, Yang L, Xu Z, Kong FS. Radiation Induced Lymphopenia Is Associated With the Effective Dose to the Circulating Immune Cells in Breast Cancer. Front Oncol. 2022;12:768956.","journal-title":"Front Oncol"},{"key":"2810_CR19","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.radonc.2019.11.014","volume":"144","author":"JY Jin","year":"2020","unstructured":"Jin JY, Mereniuk T, Yalamanchali A, Wang W, Machtay M, Spring Kong FM, Ellsworth S. A framework for modeling radiation induced lymphopenia in radiotherapy. Radiother Oncol. 2020;144:105\u201313.","journal-title":"Radiother Oncol"},{"issue":"2","key":"2810_CR20","doi-asserted-by":"publisher","first-page":"224","DOI":"10.2307\/3577549","volume":"123","author":"N Nakamura","year":"1990","unstructured":"Nakamura N, Kusunoki Y, Akiyama M. Radiosensitivity of CD4 or CD8 positive human T-lymphocytes by an in vitro colony formation assay. Radiat Res. 1990;123(2):224\u20137.","journal-title":"Radiat Res"},{"issue":"10","key":"2810_CR21","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.4049\/jimmunol.139.10.3199","volume":"139","author":"KS Sellins","year":"1987","unstructured":"Sellins KS, Cohen JJ. Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J Immunol. 1987;139(10):3199\u2013206.","journal-title":"J Immunol"},{"issue":"1","key":"2810_CR22","doi-asserted-by":"publisher","first-page":"2478","DOI":"10.1038\/s41598-021-81058-1","volume":"11","author":"D Heylmann","year":"2021","unstructured":"Heylmann D, Ponath V, Kindler T, Kaina B. Comparison of DNA repair and radiosensitivity of different blood cell populations. Sci Rep. 2021;11(1):2478.","journal-title":"Sci Rep"},{"issue":"3","key":"2810_CR23","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1002\/mp.16199","volume":"50","author":"F Liu","year":"2023","unstructured":"Liu F, Shi J, Zha H, Li G, Li A, Gu W, Hu A, Gao Q, Wang H, Zhang L, Liu J, Liu Y, Xu H, Tang C, Chen H. Development of a compact linear accelerator to generate ultrahigh dose rate high-energy X-rays for FLASH radiotherapy applications. Med Phys. 2023;50(3):1680\u201398.","journal-title":"Med Phys"},{"issue":"5","key":"2810_CR24","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0969-806X(98)00185-6","volume":"53","author":"P Geoffrey","year":"1998","unstructured":"Geoffrey P, Jacobs. A review on the effects of ionizing radiation on blood and blood components. Radiat Phys Chem. 1998;53(5):511\u201323.","journal-title":"Radiat Phys Chem"},{"issue":"3","key":"2810_CR25","first-page":"321","volume":"10","author":"D Xu","year":"2012","unstructured":"Xu D, Peng M, Zhang Z, Dong G, Zhang Y, Yu H. Study of damage to red blood cells exposed to different doses of \u03b3-ray irradiation. Blood Transfus. 2012;10(3):321\u201330.","journal-title":"Blood Transfus"},{"key":"2810_CR26","doi-asserted-by":"publisher","first-page":"669455","DOI":"10.3389\/fphys.2021.669455","volume":"12","author":"AM L\u00f3pez-Canizales","year":"2021","unstructured":"L\u00f3pez-Canizales AM, Angulo-Molina A, Garibay-Escobar A, Silva-Campa E, Mendez-Rojas MA, Santacruz-G\u00f3mez K, Acosta-El\u00edas M, Casta\u00f1eda-Medina B, Soto-Puebla D, \u00c1lvarez-Bajo O, Burgara-Estrella A, Pedroza-Montero M. Nanoscale Changes on RBC Membrane Induced by Storage and Ionizing Radiation: A Mini-Review. Front Physiol. 2021;12:669455.","journal-title":"Front Physiol"},{"issue":"1","key":"2810_CR27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.it.2006.11.002","volume":"28","author":"AM Cooper","year":"2007","unstructured":"Cooper AM, Khader SA. IL-12p40: an inherently agonistic cytokine. Trends Immunol. 2007;28(1):33\u20138.","journal-title":"Trends Immunol"},{"issue":"Pt 1","key":"2810_CR28","doi-asserted-by":"publisher","first-page":"147737","DOI":"10.1016\/j.ijbiomac.2025.147737","volume":"329","author":"K Ghasemi","year":"2025","unstructured":"Ghasemi K. C-C motif glycoprotein ligand 5 (CCL5) and its GPCR CCR5: Macromolecular game-changers in cancer biology. Int J Biol Macromol. 2025;329(Pt 1):147737.","journal-title":"Int J Biol Macromol"},{"issue":"2","key":"2810_CR29","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.ijrobp.2025.03.080","volume":"123","author":"C Beekman","year":"2025","unstructured":"Beekman C, Carrasco-Rojas N, Withrow J, Dawson R, Bolch WE, Paganetti H. Radiation-Induced Lymphopenia: In Silico Replications of Preclinical Studies Suggest Importance of Dose to Lymphoid Organs. Int J Radiat Oncol Biol Phys. 2025;123(2):550\u201362.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"2810_CR30","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.ijrobp.2023.01.054","volume":"116","author":"L McCullum","year":"2023","unstructured":"McCullum L, Shin J, Xing S, Beekman C, Schuemann J, Hong T, Duda D, Mohan R, Lin SH, Correa-Alfonso CM, Domal S, Withrow J, Bolch W, Paganetti H, Grassberger C. Predicting Severity of Radiation Induced Lymphopenia in Individual Proton Therapy Patients for Varying Dose Rate and Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations. Int J Radiat Oncol Biol Phys. 2023;116(5):1226\u201333.","journal-title":"Int J Radiat Oncol Biol Phys"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13014-026-02810-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-026-02810-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13014-026-02810-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:15:57Z","timestamp":1775819757000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13014-026-02810-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2810"],"URL":"https:\/\/doi.org\/10.1186\/s13014-026-02810-3","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"7 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 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":"All animal experiments were approved by the Animal Ethics Committee of Capital Medical University and conducted in accordance with the institutional guidelines for the care and use of laboratory animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"53"}}