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This study analyzed data from 990 eligible early-stage LUAD patients meeting the following inclusion criteria: written informed consent, absence of neoadjuvant therapy, planned surgical resection, postoperative pathological confirmation of LUAD, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Analysis of a retrospective cohort of 601 stage I LUAD patients demonstrated a significant correlation between the extent of tumor invasion and 5-year survival rates. Transcriptomic profiling revealed a progressively immunosuppressive tumor microenvironment (TME) during the AIS\/MIA-to-IAC transition, characterized by dysfunctional immune cells and diminished local anti-tumor immunity. Notably, peripheral blood analysis from 389 patients showed a significant decrease in telomerase reverse transcriptase-positive (TERT\u2009+) leukocytes with tumor progression, a change detectable earlier than circulating tumor cells (CTCs). Two-year follow-up data corroborated these findings. This study elucidates key biological events in early-stage LUAD progression, revealing that the tumor remodels both local and systemic immunity to facilitate its advancement. The reduction in peripheral TERT\u2009+\u2009leukocytes emerges as a potential non-invasive biomarker for the early detection of malignant progression, supporting the rationale for immune-based interventions at earlier disease stages.<\/jats:p>","DOI":"10.1186\/s43556-025-00383-3","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T10:28:47Z","timestamp":1766140127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Peripheral TERT- positive leukocytes as a biomarker of the local and systemic immune failure in early-stage lung adenocarcinoma progression"],"prefix":"10.1186","volume":"6","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousheng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-2751","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"issue":"1","key":"383_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel RL, Miller KD, Jemal A. 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