{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:40:24Z","timestamp":1786711224903,"version":"build-2736575974"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"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:p>Esophageal cancer is a highly aggressive malignancy with a notoriously poor prognosis. While immunotherapy, particularly immune checkpoint blockade (ICB), has revolutionized oncology, its clinical efficacy in esophageal cancer is severely limited by primary and acquired resistance. This resistance is fundamentally driven by a deeply immunosuppressive tumor microenvironment (TME), characterized by severe hypoxia, acidosis, a dense extracellular matrix (ECM), and an abundance of immunosuppressive populations such as M2-like tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Consequently, the esophageal TME manifests as an immunologically \u201ccold\u201d phenotype that actively excludes and exhausts effector T cells. Nanotechnology has emerged as a transformative paradigm to dismantle these physiological and immunological barriers. This review provides a comprehensive analysis of nanotechnology-enabled immunomodulation strategies designed to remodel the esophageal TME. We systematically explore state-of-the-art targeted nanoplatforms and highlight their specific mechanisms in TME reprogramming, including alleviating hypoxia and acidosis, repolarizing TAMs, restoring dendritic cell (DC) function, and inducing immunogenic cell death (ICD) and ferroptosis. Furthermore, we evaluate synergistic strategies that combine rationally designed nanomedicines with diverse immunotherapeutic modalities to overcome resistance. By facilitating the crucial transition from \u201ccold\u201d to \u201chot\u201d tumors, nanotechnology offers promising potential to amplify antitumor immunity and may contribute to improving clinical outcomes in esophageal cancer.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1905617","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:14:35Z","timestamp":1786709675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanotechnology-enabled immunomodulation in esophageal cancer: targeting the tumor microenvironment to overcome therapeutic barriers"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiaoyi","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/ National Clinical Research Center for Cancer\/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/ National Clinical Research Center for Cancer\/ Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, China"]},{"name":"The Affiliated Cancer Hospital, School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.01888","article-title":"Randomized phase iii keynote-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer","volume":"38","author":"Takashi","year":"2020","journal-title":"J Clin 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