{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:03:13Z","timestamp":1784872993502,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016334","name":"Jiangsu Provincial Medical Center","doi-asserted-by":"publisher","award":["JSDW202233"],"award-info":[{"award-number":["JSDW202233"]}],"id":[{"id":"10.13039\/501100016334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007289","name":"Nanjing Medical University","doi-asserted-by":"publisher","award":["GQ202207"],"award-info":[{"award-number":["GQ202207"]}],"id":[{"id":"10.13039\/501100007289","id-type":"DOI","asserted-by":"publisher"}]}],"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>Postoperative lymph node recurrence in esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and lacks standardized treatment. Radioresistance and aberrant immune\/inflammatory tumor microenvironment (TME) are major barriers limiting the efficacy of concurrent chemoradiotherapy (CRT). This study aimed to evaluate the efficacy, safety, and immune-related radiosensitising mechanisms of anlotinib combined with CRT for postoperative isolated lymph node recurrence of ESCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this single\u2212arm phase II trial, 47 patients with postoperative isolated lymph node recurrence of ESCC received anlotinib plus concurrent CRT. Tumor response and safety were assessed per RECIST version 1.1 and NCI-CTCAE version 4.0. Peripheral blood immune indicators (CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio, TNF-\u03b1, IL-6) were dynamically monitored. Transcriptomic and pathway enrichment analyses were performed in radioresistant ESCC cells to explore immune\u2212mediated radioresistance and anlotinib\u2019s regulatory mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median progression\u2212free survival (PFS) and overall survival (OS) were 20.2 and 30.7 months, respectively. The objective response rate (ORR) was 91.5% (12.8% complete response, 78.7% partial response), with a 100% disease control rate (DCR). The mean lymph node diameter reduction was 60.1 \u00b1 18.0%. Treatment was well tolerated; Grade \u2265 3 treatment\u2212related adverse events occurred in 42.6% of patients and were reversible without treatment interruption. Peripheral blood immune monitoring showed a significant increase in the CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio and marked decreases in TNF-\u03b1 and IL-6 levels after treatment (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;\u00a00.001). Transcriptomic profiling revealed that acquired radioresistance in ESCC was accompanied by prominent enrichment of immune\u2212 and inflammation\u2212related signaling pathways, including JAK-STAT, TNF, and cytosolic DNA\u2212sensing pathways. Anlotinib may enhance radiosensitivity by normalizing tumor vasculature and remodeling the immunosuppressive TME, thereby alleviating immune\u2212related radioresistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Anlotinib combined with CRT achieves favorable efficacy and manageable toxicity in postoperative nodal recurrent ESCC. This regimen significantly reshapes the peripheral immune profile and overcomes radioresistance via dual modulation of tumor vasculature and immune-inflammatory pathways. It represents a promising salvage strategy worthy of validation in multicenter randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/www.chictr.org.cn\/<\/jats:uri>\n                      , identifier ChiCTR1900023677.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1862131","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:35:48Z","timestamp":1784871348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anlotinib combined with chemoradiotherapy for postoperative isolated lymph node recurrence of ESCC: a phase II 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Affiliated Huai\u2019an No. 1 People\u2019s Hospital of Nanjing Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Huai\u2019an No. 1 People\u2019s Hospital of Nanjing Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Affiliated Huai\u2019an No.1 People\u2019s Hospital of Nanjing Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Huai\u2019an No. 1 People\u2019s Hospital of Nanjing Medical University","place":["Huai\u2019an, Jiangsu, 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