{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:49:33Z","timestamp":1782233373888,"version":"3.54.5"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472002"],"award-info":[{"award-number":["82472002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006739","name":"Capital Foundation of Medical Development","doi-asserted-by":"publisher","award":["2024-2-2157"],"award-info":[{"award-number":["2024-2-2157"]}],"id":[{"id":"10.13039\/501100006739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol Exp"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Previous studies on the immune function after radiofrequency ablation (RFA) mainly focused on the immune microenvironment in residual tumors. Thus, we investigate the impact of complete RFA (cRFA) and incomplete RFA (iRFA) on the immune microenvironment of distant tumors, determining whether combination with immunotherapy can improve outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and materials<\/jats:title>\n                    <jats:p>Using a bilateral subcutaneous CT26 murine model, one tumor underwent cRFA or iRFA while the contralateral tumor served as a distant site. Immune profiling by ribonucleic acid (RNA) sequencing, flow cytometry, and immunohistochemistry was performed at days 3 and 9 post-RFA (6 mice per group). Based on transcriptomic findings, anti-CTLA-4 therapy was evaluated following cRFA. Tumor growth and survival were additionally assessed (8 mice per group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells post-RFA increased at day 3 compared with controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049), while decreasing at day 9 after cRFA. Additionally, the ratio between pro-inflammatory and anti-inflammatory macrophages (M1\/M2) decreased at day 9 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034), suggesting an immunosuppressive microenvironment. RNA-seq demonstrated that CTLA-4 significantly upregulated 9 days after cRFA. Combined cRFA+anti-CTLA-4 increased distant tumor CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cells, and distant tumor growth in this group was significantly decreased\n                      <jats:italic>versus<\/jats:italic>\n                      cRFA alone (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Complete RFA is associated with a delayed immunosuppressive shift in distant tumors. Targeting CTLA-4 following ablation may partially mitigate this effect and enhance systemic tumor control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance statement<\/jats:title>\n                    <jats:p>The combination of anti-CTLA-4 targeted therapy and complete radiofrequency ablation demonstrated a synergistic anti-tumor immunotherapy effect, which provided a potentially better therapeutic strategy for preventing tumor recurrence after radiofrequency ablation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The RNA-seq results demonstrated that CTLA-4 was upregulated in the distant tumor on 9 days after complete radiofrequency ablation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Anti-tumor immune response initially associated with radiofrequency ablation was relatively transient, while an immunosuppressive microenvironment was formed in the distant tumor in 9 days.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Anti-CTLA-4 therapy after complete ablation significantly delayed distant tumor growth and promoted an anti-tumor immune microenvironment.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41747-026-00765-4","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:58:16Z","timestamp":1782230296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potentiation of the altered immune microenvironment following RF ablation of murine distant tumors with CTLA-4 immunotherapy"],"prefix":"10.1186","volume":"10","author":[{"given":"Kun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-8068","authenticated-orcid":false,"given":"Wei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Nahum","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"765_CR1","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1148\/radiol.12111851","volume":"265","author":"L Solbiati","year":"2012","unstructured":"Solbiati L, Ahmed M, Cova L, Ierace T, Brioschi M, Goldberg SN (2012) Small liver colorectal metastases treated with percutaneous radiofrequency ablation: local response rate and long-term survival with up to 10-year follow-up. Radiology 265:958\u2013968. https:\/\/doi.org\/10.1148\/radiol.12111851","journal-title":"Radiology"},{"key":"765_CR2","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1148\/radiol.2533081968","volume":"253","author":"MF Meloni","year":"2009","unstructured":"Meloni MF, Andreano A, Laeseke PF, Livraghi T, Sironi S, Lee FT Jr (2009) Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation-intermediate and long-term survival rates. Radiology 253:861\u2013869. https:\/\/doi.org\/10.1148\/radiol.2533081968","journal-title":"Radiology"},{"key":"765_CR3","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1148\/radiol.10081634","volume":"258","author":"M Ahmed","year":"2011","unstructured":"Ahmed M, Brace CL, Lee FT Jr, Goldberg SN (2011) Principles of and advances in percutaneous ablation. Radiology 258:351\u2013369. https:\/\/doi.org\/10.1148\/radiol.10081634","journal-title":"Radiology"},{"key":"765_CR4","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jhep.2011.12.001","volume":"56","author":"European Association for the Study of the Liver\u2013European Association for Research and Treatment of Cancer","year":"2012","unstructured":"European Association for the Study of the Liver\u2013European Association for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908\u2013943. https:\/\/doi.org\/10.1016\/j.jhep.2011.12.001","journal-title":"J Hepatol"},{"key":"765_CR5","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1148\/radiol.2343040350","volume":"234","author":"R Lencioni","year":"2005","unstructured":"Lencioni R, Cioni D, Crocetti L et al (2005) Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 234:961\u2013967. https:\/\/doi.org\/10.1148\/radiol.2343040350","journal-title":"Radiology"},{"key":"765_CR6","doi-asserted-by":"publisher","first-page":"e001038","DOI":"10.1136\/jitc-2020-001038","volume":"8","author":"X Qi","year":"2020","unstructured":"Qi X, Yang M, Ma L et al (2020) Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response. J Immunother Cancer 8:e001038. https:\/\/doi.org\/10.1136\/jitc-2020-001038","journal-title":"J Immunother Cancer"},{"key":"765_CR7","doi-asserted-by":"publisher","first-page":"e70417","DOI":"10.1371\/journal.pone.0070417","volume":"8","author":"SR Gameiro","year":"2013","unstructured":"Gameiro SR, Higgins JP, Dreher MR et al (2013) Combination therapy with local radiofrequency ablation and systemic vaccine enhances antitumor immunity and mediates local and distal tumor regression. PLoS One 8:e70417. https:\/\/doi.org\/10.1371\/journal.pone.0070417","journal-title":"PLoS One"},{"key":"765_CR8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1148\/radiol.2511072175","volume":"251","author":"SA Dromi","year":"2009","unstructured":"Dromi SA, Walsh MP, Herby S et al (2009) Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 251:58\u201366. https:\/\/doi.org\/10.1148\/radiol.2511072175","journal-title":"Radiology"},{"key":"765_CR9","first-page":"6496","volume":"63","author":"TT Wissniowski","year":"2003","unstructured":"Wissniowski TT, H\u00e4nsler J, Neureiter D et al (2003) Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res 63:6496\u20136500","journal-title":"Cancer Res"},{"key":"765_CR10","doi-asserted-by":"publisher","first-page":"1550342","DOI":"10.1080\/2162402x.2018.1550342","volume":"8","author":"K Lemdani","year":"2019","unstructured":"Lemdani K, Mignet N, Boudy V et al (2019) Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma. Oncoimmunology 8:1550342. https:\/\/doi.org\/10.1080\/2162402x.2018.1550342","journal-title":"Oncoimmunology"},{"key":"765_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51722-x","volume":"15","author":"MJ Mooradian","year":"2024","unstructured":"Mooradian MJ, Fintelmann FJ, LaSalle TJ et al (2024) Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial. Nat Commun 15:7357. https:\/\/doi.org\/10.1038\/s41467-024-51722-x","journal-title":"Nat Commun"},{"key":"765_CR12","doi-asserted-by":"publisher","first-page":"e010222","DOI":"10.1136\/jitc-2024-010222","volume":"13","author":"B Geboers","year":"2025","unstructured":"Geboers B, Timmer F, Vos D et al (2025) Systemic immunomodulation by irreversible electroporation versus stereotactic ablative body radiotherapy in locally advanced pancreatic cancer: the CROSSFIRE trial. J Immunother Cancer 13:e010222. https:\/\/doi.org\/10.1136\/jitc-2024-010222","journal-title":"J Immunother Cancer"},{"key":"765_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1000681","volume":"13","author":"J Shou","year":"2022","unstructured":"Shou J, Mo F, Zhang S et al (2022) Combination treatment of radiofrequency ablation and peptide neoantigen vaccination: promising modality for future cancer immunotherapy. Front Immunol 13:1000681. https:\/\/doi.org\/10.3389\/fimmu.2022.1000681","journal-title":"Front Immunol"},{"key":"765_CR14","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1080\/02656736.2021.1887942","volume":"38","author":"A Markezana","year":"2021","unstructured":"Markezana A, Goldberg SN, Kumar G et al (2021) Incomplete thermal ablation of tumors promotes increased tumorigenesis. Int J Hyperthermia 38:263\u2013272. https:\/\/doi.org\/10.1080\/02656736.2021.1887942","journal-title":"Int J Hyperthermia"},{"key":"765_CR15","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.jconrel.2024.10.069","volume":"376","author":"T Li","year":"2024","unstructured":"Li T, Li B, Lin L et al (2024) Anti-CTLA-4 antibody self-presented dendritic cell nanovesicles boost the immunotherapy of hepatocellular carcinoma after microwave ablation. J Control Release 376:913\u2013929. https:\/\/doi.org\/10.1016\/j.jconrel.2024.10.069","journal-title":"J Control Release"},{"key":"765_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-02170-0","volume":"21","author":"Y Cao","year":"2023","unstructured":"Cao Y, Sun T, Sun B et al (2023) Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation. J Nanobiotechnology 21:404. https:\/\/doi.org\/10.1186\/s12951-023-02170-0","journal-title":"J Nanobiotechnology"},{"key":"765_CR17","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1245\/s10434-007-9733-9","volume":"15","author":"VW Lam","year":"2008","unstructured":"Lam VW, Ng KK, Chok KS et al (2008) Incomplete ablation after radiofrequency ablation of hepatocellular carcinoma: analysis of risk factors and prognostic factors. Ann Surg Oncol 15:782\u2013790. https:\/\/doi.org\/10.1245\/s10434-007-9733-9","journal-title":"Ann Surg Oncol"},{"key":"765_CR18","doi-asserted-by":"publisher","first-page":"399","DOI":"10.15403\/jgld.2014.1121.274.pro","volume":"27","author":"Z Sparchez","year":"2018","unstructured":"Sparchez Z, Mocan T, Radu P et al (2018) Prognostic factors after percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma. Impact of incomplete ablation on recurrence and overall survival rates. J Gastrointestin Liver Dis 27:399\u2013407. https:\/\/doi.org\/10.15403\/jgld.2014.1121.274.pro","journal-title":"J Gastrointestin Liver Dis"},{"key":"765_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202403979","volume":"14","author":"D Wang","year":"2025","unstructured":"Wang D, Nie T, Fang Y et al (2025) Tailored liposomal nanomedicine suppresses incomplete radiofrequency ablation-induced tumor relapse by reprogramming antitumor immunity. Adv Healthc Mater 14:e2403979. https:\/\/doi.org\/10.1002\/adhm.202403979","journal-title":"Adv Healthc Mater"},{"key":"765_CR20","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232365","volume":"310","author":"A Shewarega","year":"2024","unstructured":"Shewarega A, Santana JG, Nam D et al (2024) Effect of incomplete cryoablation and matrix metalloproteinase inhibition on intratumoral CD8+ T-cell infiltration in murine hepatocellular carcinoma. Radiology 310:e232365. https:\/\/doi.org\/10.1148\/radiol.232365","journal-title":"Radiology"},{"key":"765_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123087","volume":"317","author":"Y Fang","year":"2025","unstructured":"Fang Y, Hu F, Ren W et al (2025) Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse. Biomaterials 317:123087. https:\/\/doi.org\/10.1016\/j.biomaterials.2025.123087","journal-title":"Biomaterials"},{"key":"765_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-22279-w","volume":"12","author":"M Mauda-Havakuk","year":"2022","unstructured":"Mauda-Havakuk M, Hawken NM, Owen JW et al (2022) Comparative analysis of the immune response to RFA and cryoablation in a colon cancer mouse model. Sci Rep 12:18229. https:\/\/doi.org\/10.1038\/s41598-022-22279-w","journal-title":"Sci Rep"},{"key":"765_CR23","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1148\/radiol.2015150787","volume":"279","author":"S Wang","year":"2016","unstructured":"Wang S, Mei XG, Goldberg SN et al (2016) Does thermosensitive liposomal vinorelbine improve end-point survival after percutaneous radiofrequency ablation of liver tumors in a mouse model? Radiology 279:762\u2013772. https:\/\/doi.org\/10.1148\/radiol.2015150787","journal-title":"Radiology"},{"key":"765_CR24","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1148\/radiol.10100500","volume":"257","author":"W Yang","year":"2010","unstructured":"Yang W, Ahmed M, Elian M et al (2010) Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model? Radiology 257:685\u2013696. https:\/\/doi.org\/10.1148\/radiol.10100500","journal-title":"Radiology"},{"key":"765_CR25","doi-asserted-by":"publisher","first-page":"694","DOI":"10.21147\/j.issn.1000-9604.2021.06.06","volume":"33","author":"S Wang","year":"2021","unstructured":"Wang S, Liu J, Wu H et al (2021) All-trans retinoic acid (ATRA) inhibits insufficient radiofrequency ablation (iRFA)-induced enrichment of tumor-initiating cells in hepatocellular carcinoma. Chin J Cancer Res 33:694\u2013707. https:\/\/doi.org\/10.21147\/j.issn.1000-9604.2021.06.06","journal-title":"Chin J Cancer Res"},{"key":"765_CR26","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1007\/s00270-020-02505-6","volume":"43","author":"L Zhang","year":"2020","unstructured":"Zhang L, Wang J, Jiang J, Zhang M, Shen J (2020) CTLA-4 blockade suppresses progression of residual tumors and improves survival after insufficient radiofrequency ablation in a subcutaneous murine hepatoma model. Cardiovasc Interv Radiol 43:1353\u20131361. https:\/\/doi.org\/10.1007\/s00270-020-02505-6","journal-title":"Cardiovasc Interv Radiol"},{"key":"765_CR27","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1158\/2326-6066.Cir-13-0031-t","volume":"2","author":"WL Redmond","year":"2014","unstructured":"Redmond WL, Linch SN, Kasiewicz MJ (2014) Combined targeting of costimulatory (OX40) and coinhibitory (CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity. Cancer Immunol Res 2:142\u2013153. https:\/\/doi.org\/10.1158\/2326-6066.Cir-13-0031-t","journal-title":"Cancer Immunol Res"},{"key":"765_CR28","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1158\/1078-0432.CCR-15-1352","volume":"22","author":"L Shi","year":"2016","unstructured":"Shi L, Chen L, Wu C et al (2016) PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor. Clin Cancer Res 22:1173\u20131184. https:\/\/doi.org\/10.1158\/1078-0432.CCR-15-1352","journal-title":"Clin Cancer Res"},{"key":"765_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13204-3","volume":"10","author":"L Shi","year":"2019","unstructured":"Shi L, Wang J, Ding N et al (2019) Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy. Nat Commun 10:5421. https:\/\/doi.org\/10.1038\/s41467-019-13204-3","journal-title":"Nat Commun"},{"key":"765_CR30","doi-asserted-by":"publisher","first-page":"4024","DOI":"10.1158\/0008-5472.CAN-03-3949","volume":"64","author":"MH den Brok","year":"2004","unstructured":"den Brok MH, Sutmuller RP, van der Voort R et al (2004) In situ tumor ablation creates an antigen source for the generation of antitumor immunity. Cancer Res 64:4024\u20134029. https:\/\/doi.org\/10.1158\/0008-5472.CAN-03-3949","journal-title":"Cancer Res"},{"key":"765_CR31","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.jhep.2005.04.016","volume":"43","author":"MY Ali","year":"2005","unstructured":"Ali MY, Grimm CF, Ritter M et al (2005) Activation of dendritic cells by local ablation of hepatocellular carcinoma. J Hepatol 43:817\u2013822. https:\/\/doi.org\/10.1016\/j.jhep.2005.04.016","journal-title":"J Hepatol"},{"key":"765_CR32","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s41747-026-00687-1","volume":"10","author":"M Stechele","year":"2026","unstructured":"Stechele M, Amadi J, Salvermoser L et al (2026) Hepatic radiofrequency ablation induces global cellular activation throughout the liver. Eur Radiol Exp 10:38. https:\/\/doi.org\/10.1186\/s41747-026-00687-1","journal-title":"Eur Radiol Exp"},{"key":"765_CR33","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1002\/hep.26153","volume":"57","author":"E Mizukoshi","year":"2013","unstructured":"Mizukoshi E, Yamashita T, Arai K et al (2013) Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology 57:1448\u20131457. https:\/\/doi.org\/10.1002\/hep.26153","journal-title":"Hepatology"},{"key":"765_CR34","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1158\/0008-5472.CAN-05-2244","volume":"66","author":"A Zerbini","year":"2006","unstructured":"Zerbini A, Pilli M, Penna A et al (2006) Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res 66:1139\u20131146. https:\/\/doi.org\/10.1158\/0008-5472.CAN-05-2244","journal-title":"Cancer Res"},{"key":"765_CR35","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1148\/radiol.2015141695","volume":"276","author":"N Rozenblum","year":"2015","unstructured":"Rozenblum N, Zeira E, Scaiewicz V et al (2015) Oncogenesis: an \u201coff-target\u201d effect of radiofrequency ablation. Radiology 276:426\u2013432. https:\/\/doi.org\/10.1148\/radiol.2015141695","journal-title":"Radiology"},{"key":"765_CR36","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2018.11.043","volume":"176","author":"H Li","year":"2019","unstructured":"Li H, van der Leun AM, Yofe I et al (2019) Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176:775\u2013789.e718. https:\/\/doi.org\/10.1016\/j.cell.2018.11.043","journal-title":"Cell"},{"key":"765_CR37","doi-asserted-by":"publisher","first-page":"e001136","DOI":"10.1136\/jitc-2020-001136","volume":"9","author":"M Yang","year":"2021","unstructured":"Yang M, Lu J, Zhang G et al (2021) CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer. J Immunother Cancer 9:e001136. https:\/\/doi.org\/10.1136\/jitc-2020-001136","journal-title":"J Immunother Cancer"},{"key":"765_CR38","doi-asserted-by":"publisher","first-page":"8755","DOI":"10.26355\/eurrev_201812_16641","volume":"22","author":"JJ Ma","year":"2018","unstructured":"Ma JJ, Jiang L, Tong DY, Ren YN, Sheng MF, Liu HC (2018) CXCL13 inhibition induce the apoptosis of MDA-MB-231 breast cancer cells through blocking CXCR5\/ERK signaling pathway. Eur Rev Med Pharmacol Sci 22:8755\u20138762. https:\/\/doi.org\/10.26355\/eurrev_201812_16641","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"765_CR39","doi-asserted-by":"publisher","first-page":"9293","DOI":"10.3892\/ol.2018.8510","volume":"15","author":"L Xu","year":"2018","unstructured":"Xu L, Liang Z, Li S, Ma J (2018) Signaling via the CXCR5\/ERK pathway is mediated by CXCL13 in mice with breast cancer. Oncol Lett 15:9293\u20139298. https:\/\/doi.org\/10.3892\/ol.2018.8510","journal-title":"Oncol Lett"},{"key":"765_CR40","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1080\/02656736.2021.1991011","volume":"38","author":"X Wang","year":"2021","unstructured":"Wang X, Liu G, Chen S et al (2021) Combination therapy with PD-1 blockade and radiofrequency ablation for recurrent hepatocellular carcinoma: a propensity score matching analysis. Int J Hyperthermia 38:1519\u20131528. https:\/\/doi.org\/10.1080\/02656736.2021.1991011","journal-title":"Int J Hyperthermia"},{"key":"765_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115351","volume":"166","author":"T Sun","year":"2023","unstructured":"Sun T, Sun B, Cao Y et al (2023) Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma. Biomed Pharmacother 166:115351. https:\/\/doi.org\/10.1016\/j.biopha.2023.115351","journal-title":"Biomed Pharmacother"},{"key":"765_CR42","doi-asserted-by":"publisher","first-page":"20311","DOI":"10.1002\/cam4.6602","volume":"12","author":"Z Wen","year":"2023","unstructured":"Wen Z, Wang J, Tu B et al (2023) Radiofrequency ablation combined with toripalimab for recurrent hepatocellular carcinoma: a prospective controlled trial. Cancer Med 12:20311\u201320320. https:\/\/doi.org\/10.1002\/cam4.6602","journal-title":"Cancer Med"},{"key":"765_CR43","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","volume":"131","author":"B Rowshanravan","year":"2018","unstructured":"Rowshanravan B, Halliday N, Sansom DM (2018) CTLA-4: a moving target in immunotherapy. Blood 131:58\u201367. https:\/\/doi.org\/10.1182\/blood-2017-06-741033","journal-title":"Blood"},{"key":"765_CR44","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111556","volume":"42","author":"A Kennedy","year":"2023","unstructured":"Kennedy A, Robinson MA, Hinze C et al (2023) The CTLA-4 immune checkpoint protein regulates PD-L1:PD-1 interaction via transendocytosis of its ligand CD80. EMBO J 42:e111556. https:\/\/doi.org\/10.15252\/embj.2022111556","journal-title":"EMBO J"},{"key":"765_CR45","doi-asserted-by":"publisher","DOI":"10.1080\/02656736.2024.2373319","volume":"41","author":"J Gu","year":"2024","unstructured":"Gu J, Yu Z, Tang X, Chen W, Deng X, Zhu X (2024) Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice. Int J Hyperthermia 41:2373319. https:\/\/doi.org\/10.1080\/02656736.2024.2373319","journal-title":"Int J Hyperthermia"},{"key":"765_CR46","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1016\/j.jvir.2020.01.022","volume":"31","author":"L Zhang","year":"2020","unstructured":"Zhang L, Xu L, Wang Y, Liu X, Zhang M, Li W (2020) Antitumor immunity augmented by combining radiofrequency ablation with anti-CTLA-4 therapy in a subcutaneous murine hepatoma model. J Vasc Interv Radiol 31:1178\u20131186. https:\/\/doi.org\/10.1016\/j.jvir.2020.01.022","journal-title":"J Vasc Interv Radiol"},{"key":"765_CR47","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jhep.2016.10.029","volume":"66","author":"AG Duffy","year":"2017","unstructured":"Duffy AG, Ulahannan SV, Makorova-Rusher O et al (2017) Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 66:545\u2013551. https:\/\/doi.org\/10.1016\/j.jhep.2016.10.029","journal-title":"J Hepatol"}],"container-title":["European Radiology Experimental"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41747-026-00765-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41747-026-00765-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41747-026-00765-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:58:18Z","timestamp":1782230298000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41747-026-00765-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["765"],"URL":"https:\/\/doi.org\/10.1186\/s41747-026-00765-4","relation":{},"ISSN":["2509-9280"],"issn-type":[{"value":"2509-9280","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"assertion":[{"value":"10 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal experiments were approved by the Peking University Cancer Hospital Animal Care and Use Committee, code EAEC 2024-32(2024-11).","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 that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"97"}}