{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T11:25:52Z","timestamp":1789298752653,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Radiotherapy (RT) has traditionally been considered a local treatment modality; however, accumulating evidence suggests that it can induce systemic antitumor responses outside the irradiated field. The classical abscopal effect, defined as the regression of non-irradiated tumor lesions following localized RT, has gained renewed attention in the era of immune checkpoint inhibitors (ICIs). Preclinical and clinical studies have demonstrated that RT can promote immunogenic cell death, antigen presentation, cytokine release, and adaptive immune activation, processes that may contribute to systemic antitumor immunity, particularly when combined with ICIs. Clinically apparent abscopal responses remain rare and heterogeneous, and the biological mechanisms underlying these phenomena are not completely understood. Systemic tumor regression has occasionally been observed in clinical settings that do not involve checkpoint blockade, including RT alone, chemotherapy-containing regimens, and central nervous system-directed therapies. These findings suggest that radiation-associated systemic antitumor responses may arise through overlapping immunologic mechanisms involving both innate and adaptive immunity, tumor microenvironment remodeling, and treatment-associated cellular stress. This review summarizes the current clinical evidence and biological mechanisms underlying radiation-associated systemic antitumor responses and discusses emerging concepts extending beyond the conventional RT\u2013immunotherapy paradigm. We further examined unresolved challenges, including treatment heterogeneity, biomarker limitations, pseudoprogression, and difficulties in mechanistic confirmation. Finally, we propose that the broader \u201cbeyond-abscopal\u201d framework may serve as a hypothesis-generating conceptual model for investigating systemic tumor responses across diverse treatment contexts while emphasizing the need for cautious interpretation and prospective translational validation.<\/jats:p>","DOI":"10.3390\/cancers18132098","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Radiotherapy-Associated Systemic Antitumor Responses Beyond the Classical Abscopal Paradigm"],"prefix":"10.3390","volume":"18","author":[{"given":"Yosuke","family":"Dotsu","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5487-0453","authenticated-orcid":false,"given":"Kazumasa","family":"Akagi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"},{"name":"Clinical Oncology Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritaka","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6143-1205","authenticated-orcid":false,"given":"Midori","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"},{"name":"Clinical Research Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"},{"name":"Clinical Oncology Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-0618","authenticated-orcid":false,"given":"Shinnosuke","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Mukae","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagasaki Harbor Medical Center, Nagasaki 850-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1001\/jamaoncol.2015.2756","article-title":"Role of Local Radiation Therapy in Cancer Immunotherapy","volume":"1","author":"Demaria","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13073-019-0653-7","article-title":"Radiation therapy and anti-tumor immunity: Exposing immunogenic mutations to the immune system","volume":"11","author":"Lhuillier","year":"2019","journal-title":"Genome Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.semradonc.2014.07.005","article-title":"Radiotherapy and immunogenic cell death","volume":"25","author":"Golden","year":"2015","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/nm1622","article-title":"Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy","volume":"13","author":"Apetoh","year":"2007","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032712-100008","article-title":"Immunogenic cell death in cancer therapy","volume":"31","author":"Kroemer","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e498","DOI":"10.1016\/S1470-2045(15)00007-8","article-title":"Radiation and checkpoint blockade immunotherapy: Radiosensitisation and potential mechanisms of synergy","volume":"16","author":"Sharabi","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1259\/0007-1285-26-305-234","article-title":"Whole body irradiation\u2014Radiobiology or medicine?","volume":"26","author":"Mole","year":"1953","journal-title":"Br. J. Radiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ctrv.2015.03.011","article-title":"The abscopal effect of local radiotherapy: Using immunotherapy to make a rare event clinically relevant","volume":"41","author":"Reynders","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.canlet.2013.09.018","article-title":"Abscopal effects of radiation therapy: A clinical review for the radiobiologist","volume":"356","author":"Siva","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"925","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":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1158\/2326-6066.CIR-13-0115","article-title":"An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer","volume":"1","author":"Golden","year":"2013","journal-title":"Cancer Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nrc.2018.6","article-title":"Using immunotherapy to boost the abscopal effect","volume":"18","author":"Ngwa","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Iwanaga, M., Dotsu, Y., Hiu, T., Ueki, N., Hirano, Y., Tokito, T., Morikawa, T., Kaneko, S., Honda, N., and Akagi, K. (2026). Regression of a Non-Irradiated Lung Adenocarcinoma During Glioblastoma-Directed Chemoradiotherapy: A Case Report. Curr. Oncol., 33.","DOI":"10.3390\/curroncol33040188"},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.medj.2023.02.003","article-title":"The abscopal effect in patients with cancer receiving immunotherapy","volume":"4","author":"Nelson","year":"2023","journal-title":"Med"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrclinonc.2016.211","article-title":"Radiotherapy and immunotherapy: A beneficial liaison?","volume":"14","author":"Weichselbaum","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Alard","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nm1523","article-title":"Calreticulin exposure dictates the immunogenicity of cancer cell death","volume":"13","author":"Obeid","year":"2007","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1158\/1078-0432.CCR-09-2891","article-title":"Immunogenic tumor cell death for optimal anticancer therapy: The calreticulin exposure pathway","volume":"16","author":"Zitvogel","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4049\/jimmunol.1200563","article-title":"Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation","volume":"189","author":"Gupta","year":"2012","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1158\/2326-6066.CIR-15-0253","article-title":"Antitumor Efficacy of Radiation plus Immunotherapy Depends upon Dendritic Cell Activation of Effector CD8+ T Cells","volume":"4","author":"Dovedi","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.3389\/fimmu.2018.03059","article-title":"Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment","volume":"9","author":"Fu","year":"2018","journal-title":"Front Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1084\/jem.20052494","article-title":"Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy","volume":"203","author":"Reits","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI67313","article-title":"Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice","volume":"124","author":"Deng","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nrc3958","article-title":"The tumour microenvironment after radiotherapy: Mechanisms of resistance and recurrence","volume":"15","author":"Barker","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrc3237","article-title":"Combining immunotherapy and targeted therapies in cancer treatment","volume":"12","author":"Vanneman","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1667\/RR2773.1","article-title":"Radiation-induced vascular damage in tumors: Implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS)","volume":"177","author":"Park","year":"2012","journal-title":"Radiat. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Demaria, S., and Formenti, S.C. (2012). Radiation as an immunological adjuvant: Current evidence on dose and fractionation. Front. Oncol., 2.","DOI":"10.3389\/fonc.2012.00153"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.ccell.2025.02.024","article-title":"PAI-1-driven SFRP2","volume":"43","author":"Zhang","year":"2025","journal-title":"Cancer Cell."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jnci\/djs629","article-title":"Combining radiotherapy and cancer immunotherapy: A paradigm shift","volume":"105","author":"Formenti","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.immuni.2014.10.017","article-title":"STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors","volume":"41","author":"Woo","year":"2014","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e200465","DOI":"10.1172\/JCI200465","article-title":"cGAS\/STING-mediated \u03b3\u03b4 T cell recruitment drives radioresistance: Implications for improving radioimmunotherapy outcomes","volume":"135","author":"Braman","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S1470-2045(03)01191-4","article-title":"Effects of radiation on normal tissue: Consequences and mechanisms","volume":"4","author":"Stone","year":"2003","journal-title":"Lancet Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.semradonc.2014.07.007","article-title":"Radiation and inflammation","volume":"25","author":"Schaue","year":"2015","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and Cancer: Triggers, Mechanisms, and Consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune Checkpoint Blockade in Cancer Therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1158\/0008-5472.CAN-14-1258","article-title":"Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade","volume":"74","author":"Dovedi","year":"2014","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ijrobp.2003.09.012","article-title":"Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated","volume":"58","author":"Demaria","year":"2004","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature14292","article-title":"Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer","volume":"520","author":"Rech","year":"2015","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e002038","DOI":"10.1136\/jitc-2020-002038","article-title":"Radiation dose and fraction in immunotherapy: One-size regimen does not fit all settings, so how does one choose?","volume":"9","author":"Demaria","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1056\/NEJMoa1709937","article-title":"Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer","volume":"377","author":"Antonia","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1056\/NEJMoa1809697","article-title":"Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC","volume":"379","author":"Antonia","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1200\/JCO.21.01308","article-title":"Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer","volume":"40","author":"Spigel","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zhong, W., Luo, Y., and Wu, C. (2023). The timing of durvalumab administration affects the risk of pneumonitis in patients with locally advanced non-small cell lung cancer: A systematic review and meta-analysis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11472-3"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1001\/jamaoncol.2021.2301","article-title":"Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial","volume":"7","author":"Jabbour","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","article-title":"Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody","volume":"15","author":"Dewan","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1001\/jamaoncol.2019.1478","article-title":"Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs. Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial","volume":"5","author":"Theelen","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S2213-2600(20)30391-X","article-title":"Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: A pooled analysis of two randomised trials","volume":"9","author":"Theelen","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106070","DOI":"10.1016\/j.esmoop.2026.106070","article-title":"Real-world 5-year outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC","volume":"11","author":"Girard","year":"2026","journal-title":"ESMO Open"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1200\/JCO-25-00036","article-title":"Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer: The Phase III PACIFIC-2 Study","volume":"43","author":"Bradley","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0140-6736(24)01808-7","article-title":"Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11\/GOG-3047\/KEYNOTE-A18): Overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"404","author":"Lorusso","year":"2024","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0140-6736(25)01850-1","article-title":"Nivolumab added to cisplatin and radiotherapy versus cisplatin and radiotherapy alone after surgery for people with squamous cell carcinoma of the head and neck at a high risk of relapse (GORTEC 2018-01 NIVOPOST-OP): A randomised, open-label, phase 3 trial","volume":"407","author":"Bourhis","year":"2026","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100808","DOI":"10.1016\/j.iotech.2024.100808","article-title":"650 Checkmate 73L: Phase III study comparing nivolumab (N)+concurrent chemoradiotherapy (CCRT) followed by N\u00b1ipilimumab (I) v CCRT followed by durvalumab (D) for previously untreated, locally advanced stage (stg) III NSCLC","volume":"24","author":"Peters","year":"2024","journal-title":"Immuno-Oncol. Technol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1016\/j.cllc.2021.07.005","article-title":"CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer","volume":"23","author":"Ramalingam","year":"2022","journal-title":"Clin. Lung Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJMoa2402614","article-title":"Osimertinib after Chemoradiotherapy in Stage III","volume":"391","author":"Lu","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00401-016-1606-5","article-title":"Vascular, glial, and lymphatic immune gateways of the central nervous system","volume":"132","author":"Engelhardt","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1158\/1078-0432.CCR-09-3106","article-title":"NABTT CNS Consortium. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States","volume":"16","author":"Grossman","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11060-017-2580-z","article-title":"Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide","volume":"135","author":"Campian","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e1434464","DOI":"10.1080\/2162402X.2018.1434464","article-title":"Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma","volume":"7","author":"Suryadevara","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41571-018-0003-5","article-title":"Current state of immunotherapy for glioblastoma","volume":"15","author":"Lim","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1158\/2326-6066.CIR-15-0064","article-title":"The interplay of immunotherapy and chemotherapy: Harnessing potential synergies","volume":"3","author":"Emens","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1093\/neuonc\/noy072","article-title":"Temozolomide for immunomodulation in the treatment of glioblastoma","volume":"20","author":"Karachi","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2217\/cns.12.14","article-title":"Severity, etiology and possible consequences of treatment-related lymphopenia in patients with newly diagnosed high-grade gliomas","volume":"1","author":"Yovino","year":"2012","journal-title":"CNS Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S1470-2045(08)70125-6","article-title":"Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas","volume":"9","author":"Brandsma","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1200\/JCO.23.01059","article-title":"RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults","volume":"41","author":"Wen","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_71","first-page":"e29620","article-title":"A Review of the Abscopal Effect in the Era of Immunotherapy","volume":"14","author":"Nabrinsky","year":"2022","journal-title":"Cureus"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1758835920926822","DOI":"10.1177\/1758835920926822","article-title":"A review of radiation-induced lymphopenia in patients with esophageal cancer: An immunological perspective for radiotherapy","volume":"12","author":"Wang","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ccell.2020.10.001","article-title":"The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker","volume":"39","author":"Jardim","year":"2021","journal-title":"Cancer Cell."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e005854","DOI":"10.1136\/jitc-2022-005854","article-title":"Changes in circulating tumor DNA and outcomes in solid tumors treated with immune checkpoint inhibitors: A systematic review","volume":"11","author":"Wilson","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1200\/JCO.2018.79.0006","article-title":"Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer","volume":"36","author":"Arbour","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1158\/2326-6066.CIR-17-0134","article-title":"Radiotherapy and CTLA-4 Blockade Shape the TCR Repertoire of Tumor-Infiltrating T Cells","volume":"6","author":"Rudqvist","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/s43018-025-01018-w","article-title":"Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer","volume":"6","author":"Huang","year":"2025","journal-title":"Nat. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.jtho.2024.06.024","article-title":"Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC","volume":"19","author":"Jun","year":"2024","journal-title":"J. Thorac. 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