{
  "abstract": "Tyrosine kinase inhibitors (TKIs) have transformed the treatment of EGFR-mutant non-small cell lung cancer (NSCLC), yet acquired resistance remains a major clinical limitation. Resistance is increasingly understood as an evolving state shaped not only by tumor-cell genomic alterations but also by treatment-induced remodeling of the tumor immune microenvironment (TIME). This Review examines how EGFR-TKI exposure reshapes macrophage states, T-cell function and localization, fibroblast and myeloid niches, and vascular architecture, and how these changes are reinforced by immune-checkpoint adaptation, metabolic reprogramming, and phenotypic plasticity. We then connect the evolving TIME to post-TKI therapeutic strategies according to the maturity of the supporting evidence, including immune checkpoint inhibitor-containing regimens, anti-angiogenic combinations, mechanism-matched targeted therapy, antibody-drug conjugates, bispecific T-cell engagers, and selected preclinical microenvironment-directed approaches. Finally, we discuss circulating biomarkers, single-cell sequencing, and spatial profiling as tools for longitudinally defining resistant immune states. Viewing TKI resistance as a temporally evolving immune ecosystem provides a framework for linking resistance mechanism, immune phenotype, and treatment selection rather than treating progression as a purely genomic endpoint.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Biyuan Luo"
    },
    {
      "name": "Alifujiang Hairulajiang"
    },
    {
      "name": "Jiayi Liu"
    },
    {
      "name": "Xianling Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1r4cg2x4g1c5s.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1990429",
  "fulltext_url": null,
  "id": "1r4cg2x4g1c5s",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990429",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1r4cg2x4g1c5s.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T18:20:17Z",
      "native_id": "10.3389/fimmu.2026.1990429",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990429"
    },
    {
      "first_seen": "2026-11-10T00:21:33Z",
      "native_id": "10.3389/fimmu.2026.1990429",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1990429/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "The evolving immune ecosystem of TKI resistance in EGFR-mutant NSCLC: from treatment-induced remodeling to mechanism-guided therapy",
  "title_text": "The evolving immune ecosystem of TKI resistance in EGFR-mutant NSCLC: from treatment-induced remodeling to mechanism-guided therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:33Z",
  "url": "https://research.draconitic.com/paper/1r4cg2x4g1c5s",
  "venue": "Frontiers in Immunology",
  "versions": []
}