{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:16Z","timestamp":1784700376481,"version":"3.55.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>Inhibitor of differentiation 1 (ID1) has emerged as a crucial regulator in the pathogenesis and progression of lung cancer, influencing various aspects of tumor biology, including tumor cell proliferation, invasion, metastasis, and immune modulation, within the complex tumor microenvironment. This review comprehensively examines the molecular mechanisms by which ID1 contributes to lung cancer, emphasizing its role in driving these processes. Despite significant advancements in lung cancer biology, the interactions between tumor cells and their surrounding microenvironment remain incompletely understood. This presents challenges for developing effective therapeutic strategies. We then examine the pathophysiology of malignant pleural effusion (MPE), a devastating complication of advanced lung cancer. Based on the striking mechanistic overlap between ID1-driven processes and the core drivers of MPE\u2014vascular hyperpermeability, immunosuppression, and tumor cell seeding\u2014we propose a unifying, testable hypothesis that ID1 may act as aputative key orchestrator of MPE formation, a proposition that currently awaits direct experimental validation. While direct evidence is currently lacking, we outline indirect clues and propose specific experimental approaches to test this hypothesis. By integrating recent findings from both basic research and clinical studies, this article emphasizes ID1 as a pivotal mediator in lung tumorigenesis and microenvironment remodeling. It also highlights its potential as a novel biomarker and therapeutic target, aiming to promote the development of improved diagnostic and therapeutic approaches for lung cancer, particularly in addressing challenges related to tumor progression and MPE.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1743032","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:51:51Z","timestamp":1784699511000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibitor of DNA binding 1 in lung cancer and the tumor microenvironment: a testable hypothesis for malignant pleural effusion formation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yan","family":"She","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Zhoushan Hospital","place":["Zhoushan, Zhejiang, China"]},{"name":"Department of Cardiothoracic Surgery, Jiamusi University","place":["Jiamusi, Heilongjiang, 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