{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:30:22Z","timestamp":1771399822610,"version":"3.50.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiotherapy (RT) can enhance immune control of distant metastases, known as the abscopal effect (AE), but it doesn\u2019t significantly alter the immunosuppressive tumor microenvironment (TME), resulting in low AE incidence. Combining RT with immunotherapy (especially anti-PD-1\/PD-L1 agents) has increased AE occurrences, though questions remain about this approach, particularly in tumors with low immunogenicity such as thymic squamous cell carcinoma (TSCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case description<\/jats:title>\n                    <jats:p>A 73-year-old woman with advanced TSCC and multiple metastases experienced disease progression after two therapies. Following palliative conventional fractionated radiotherapy (CFRT) (40Gy) for thoracic metastases, her pleural lesions outside the radiation field significantly reduced, indicating an AE. Despite subsequent immunotherapy and antiangiogenic drugs, treatment efficacy was unsatisfactory due to severe lymphopenia, possibly contributing to disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The rise of immunotherapy challenges traditional RT. To enhance AE occurrence in practice, factors like radiation dose, irradiation site, timing with ICIs, ICI drug choice, patient health, disease stage, and tumor traits must be considered. This case demonstrates that CFRT can induce an AE in TSCC but also highlights the associated risk of severe lymphopenia that may limit its durability. Monitoring and mitigating lymphopenia are crucial in optimizing combined therapy outcomes. This case provides new clinical evidence for treating recurrent TSCC with combined therapy, though more research on its immunological mechanisms is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1733066","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:04Z","timestamp":1771397764000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Abscopal effect induced by conventional fractionated radiotherapy following anti-PD-1 immunotherapy in pulmonary metastatic thymic squamous cell carcinoma: a case report and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Minghui","family":"Cui","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong First Medical University","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oncology, Zhangqiu People\u2019s Hospital","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong First Medical University","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0232-2","article-title":"Radiotherapy induces responses of lung cancer to CTLA-4 blockade","volume":"24","author":"Formenti","year":"2018","journal-title":"Nat Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.currproblcancer.2015.10.001","article-title":"Systematic review of case reports on the abscopal effect","volume":"40","author":"Abuodeh","year":"2016","journal-title":"Curr Probl Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112824","article-title":"Immunologic correlates of the abscopal effect in a patient with melanoma","volume":"366","author":"Postow","year":"2012","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70569-2","article-title":"Radiotherapy for renal-cell carcinoma","volume":"15","author":"De Meerleer","year":"2014","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41392-022-01102-y","article-title":"Radiotherapy combined with immunotherapy: the dawn of cancer treatment","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6871","article-title":"Advances in radiotherapy and implications for the next century: a historical perspective","volume":"69","author":"Connell","year":"2009","journal-title":"Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.12.015","article-title":"Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC-an update from the PACIFIC trial","volume":"16","author":"Faivre-Finn","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12348","article-title":"Pivotal roles of tumor-draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy","volume":"42","author":"Liu","year":"2022","journal-title":"Cancer Commun (Lond)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6410","DOI":"10.1038\/s41467-020-19917-0","article-title":"Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy","volume":"11","author":"Wisdom","year":"2020","journal-title":"Nat Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1149747","article-title":"Evaluation of triple negative breast cancer with heterogeneous immune infiltration","volume":"14","author":"Quintana","year":"2023","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41419-021-03539-5","article-title":"Epigenetic regulation of p62\/SQSTM1 overcomes the radioresistance of head and neck cancer cells via autophagy-dependent senescence induction","volume":"12","author":"Lee","year":"2021","journal-title":"Cell Death Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001615","article-title":"Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts","volume":"9","author":"Woolaver","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"13664","DOI":"10.1038\/srep13664","article-title":"Characteristics of tumor infiltrating lymphocyte and circulating lymphocyte repertoires in pancreatic cancer by the sequencing of T cell receptors","volume":"5","author":"Bai","year":"2015","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.596493","article-title":"Intratumor heterogeneity correlates with reduced immune activity and worse survival in melanoma patients","volume":"10","author":"Lin","year":"2020","journal-title":"Front Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2016.08.003","article-title":"Spatial and temporal clonal evolution during development of metastatic urothelial carcinoma","volume":"10","author":"Thomsen","year":"2016","journal-title":"Mol Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30157-3","article-title":"Integration of radiotherapy and immunotherapy for treatment of oligometastases","volume":"20","author":"Pitroda","year":"2019","journal-title":"Lancet Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1001\/jamaoncol.2018.7098","article-title":"Assessment of blood tumor mutational burden as a potential biomarker for immunotherapy in patients with non-small cell lung cancer with use of a next-generation sequencing cancer gene panel","volume":"5","author":"Wang","year":"2019","journal-title":"JAMA Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.ccell.2018.01.003","article-title":"The integrated genomic landscape of thymic epithelial tumors","volume":"33","author":"Radovich","year":"2018","journal-title":"Cancer Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30062-7","article-title":"Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study","volume":"19","author":"Giaccone","year":"2018","journal-title":"Lancet Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3016","article-title":"A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors","volume":"46","author":"Petrini","year":"2014","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.5301\/tj.5000616","article-title":"Review of the mechanisms involved in the abscopal effect and future directions with a focus on thymic carcinoma","volume":"103","author":"Lesueur","year":"2017","journal-title":"Tumori"},{"key":"B22","article-title":"Abscopal effect of local irradiation treatment for thymoma: a case report","volume":"12","author":"Guan","year":"2020","journal-title":"Am J Transl Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15297","article-title":"Impacts of the STING-IFNAR1-STAT1-IRF1 pathway on the cellular immune reaction induced by fractionated irradiation","volume":"113","author":"Du","year":"2022","journal-title":"Cancer Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"166789","DOI":"10.1016\/j.bbadis.2023.166789","article-title":"Exploring low-dose radiotherapy to overcome radio-immunotherapy resistance","volume":"1869","author":"Wang","year":"2023","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.05.002","article-title":"Radiotherapy: changing the game in immunotherapy","volume":"2","author":"Demaria","year":"2016","journal-title":"Trends Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.3390\/cancers14133273","article-title":"HIF-1alpha inhibition improves anti-tumor immunity and promotes the efficacy of stereotactic ablative radiotherapy (SABR)","volume":"14","author":"Song","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.39","article-title":"T-cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer","volume":"10","author":"He","year":"2020","journal-title":"Clin Transl Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00456-0","article-title":"Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect","volume":"3","author":"Nishiga","year":"2022","journal-title":"Nat Cancer"},{"key":"B29","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1748-717X-9-98","article-title":"Thorax irradiation triggers a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells","volume":"9","author":"Wirsdorfer","year":"2014","journal-title":"Radiat Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Vanpouille-Box","year":"2017","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08994-0","article-title":"Radiation-induced amphiregulin drives tumour metastasis","volume":"643","author":"Piffko","year":"2025","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: from mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004939","article-title":"Low-dose irradiation for reversing immunotherapy resistance: how to translate","volume":"10","author":"Ochoa-de-Olza","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S126016","article-title":"Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer","volume":"12","author":"Zhang","year":"2017","journal-title":"Int J Nanomedicine"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2020.05.002","article-title":"Effect of low-dose radiation therapy on abscopal responses to hypofractionated radiation therapy and anti-PD1 in mice and patients with non-small cell lung cancer","volume":"108","author":"Yin","year":"2020","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0003","article-title":"Low-dose radiotherapy reverses tumor immune desertification and resistance to immunotherapy","volume":"12","author":"Herrera","year":"2022","journal-title":"Cancer Discov"},{"key":"B37","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13045-020-00940-z","article-title":"SBRT combined with PD-1\/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges","volume":"13","author":"Chen","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"100909","DOI":"10.1016\/j.adro.2022.100909","article-title":"A patient-level data meta-analysis of the abscopal effect","volume":"7","author":"Hatten","year":"2022","journal-title":"Adv Radiat Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00004","article-title":"Hypofractionated irradiation suppressed the off-target mouse hepatocarcinoma growth by inhibiting myeloid-derived suppressor cell-mediated immune suppression","volume":"10","author":"Chen","year":"2020","journal-title":"Front Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/adf58f","article-title":"Geometric optimization of dose distribution in spatially fractionated radiation therapy","volume":"70","author":"Hosseinian","year":"2025","journal-title":"Phys Med Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3857\/roj.2018.00332","article-title":"Novel biological strategies to enhance the radiation therapeutic ratio","volume":"36","author":"Kim","year":"2018","journal-title":"Radiat Oncol J"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092454","article-title":"Tumor masses support naive T cell infiltration, activation, and differentiation into effectors","volume":"207","author":"Thompson","year":"2010","journal-title":"J Exp Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000867","article-title":"Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy","volume":"8","author":"Buchwald","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s12885-019-5566-8","article-title":"Abscopal effect of radiation on multiple lung metastases of lung adenocarcinoma: a case report","volume":"19","author":"Kuroda","year":"2019","journal-title":"BMC Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01126-1","article-title":"CAR T-cell therapy in autoimmune diseases","volume":"402","author":"Schett","year":"2023","journal-title":"Lancet"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2402730","article-title":"Aggressive lymphoma after CD19 CAR T-cell therapy","volume":"391","author":"Kobbe","year":"2024","journal-title":"N Engl J Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3322\/caac.21702","article-title":"Critical care management of chimeric antigen receptor T-cell therapy recipients","volume":"72","author":"Shimabukuro-Vornhagen","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00746-3","article-title":"CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study","volume":"404","author":"Frank","year":"2024","journal-title":"Lancet"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3451","article-title":"Checkpoint Antibodies but not T Cell-Recruiting Diabodies Effectively Synergize with TIL-Inducing gamma-Irradiation","volume":"76","author":"Hettich","year":"2016","journal-title":"Cancer Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.08.019","article-title":"A phase 1 trial of concurrent or sequential ipilimumab, nivolumab, and stereotactic body radiotherapy in patients with stage IV NSCLC study","volume":"17","author":"Bestvina","year":"2022","journal-title":"J Thorac Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25746","article-title":"Immunologically effective dose: a practical model for immuno-radiotherapy","volume":"9","author":"Serre","year":"2018","journal-title":"Oncotarget"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15384047.2016.1264541","article-title":"Abscopal regression following SABR for non-small-cell-lung cancer: A case report","volume":"18","author":"Cong","year":"2017","journal-title":"Cancer Biol Ther"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2229-5","article-title":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","volume":"581","author":"Yamamoto","year":"2020","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/s41419-020-03221-2","article-title":"Detection of immunogenic cell death and its relevance for cancer therapy","volume":"11","author":"Fucikova","year":"2020","journal-title":"Cell Death Dis"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1131-x","article-title":"Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination","volume":"27","author":"Yu","year":"2021","journal-title":"Nat Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0581","article-title":"Exosomes shuttle TREX1-sensitive IFN-stimulatory dsDNA from irradiated cancer cells to DCs","volume":"6","author":"Diamond","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-031920-093932","article-title":"Opposing roles of type I interferons in cancer immunity","volume":"16","author":"Boukhaled","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/j.cell.2016.11.022","article-title":"Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade","volume":"167","author":"Benci","year":"2016","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.coi.2021.02.009","article-title":"Inborn errors of STAT1 immunity","volume":"72","author":"Mizoguchi","year":"2021","journal-title":"Curr Opin Immunol"},{"key":"B61","article-title":"Combined application strategies of radiotherapy and immunotherapy [conference presentation]","volume-title":"Proceedings of the 28th Annual Meeting of the Chinese Society of Clinical Oncology (CSCO)","author":"Chen","year":"2025"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1733066\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:05Z","timestamp":1771397765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1733066\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":61,"alternative-id":["10.3389\/fimmu.2026.1733066"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1733066","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1733066"}}