{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:47:04Z","timestamp":1785836824067,"version":"3.56.0"},"reference-count":100,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova"},{"id":[{"id":"https:\/\/ror.org\/031d5vw30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Lung cancer remains the leading cause of cancer-related mortality worldwide, and durable benefit from immune checkpoint inhibitors is limited by immune exclusion, microenvironmental immunosuppression, and toxicity. This narrative translational review evaluates whether endobronchial intratumoral delivery of immuno- and gene-based therapies can transform bronchoscopic access into a therapeutic platform linking local tumour intervention with systemic antitumour immunity. We synthesise evidence on endobronchial ultrasound, electromagnetic navigation bronchoscopy, and robotic-assisted bronchoscopy, together with local checkpoint blockade, cytokine and mRNA-lipid nanoparticle constructs, oncolytic virotherapy, dendritic-cell approaches, viral and non-viral gene transfer, and enzyme- or metabolite-based strategies. Current clinical evidence remains preliminary, consisting mainly of Phase I trials, small prospective cohorts, and case-based signals, with feasibility and safety observations but no completed randomised trial demonstrating efficacy against standard-of-care systemic therapy. The most plausible candidates are patients with advanced or recurrent NSCLC, bronchoscopically accessible lesions, inadequate response to systemic immunotherapy, and immune-excluded or locally immunosuppressed tumours. Biomarkers such as PD-L1, tumour mutational burden, CD8+ infiltration, tertiary lymphoid structures, radiomics, and circulating tumour DNA require validation. This review integrates delivery technology, immune mechanisms, statistical evidence appraisal, biomarker limitations, AI-guided planning, and global feasibility.<\/jats:p>","DOI":"10.3390\/ijms27156988","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"6988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endobronchial Intratumoral Immuno- and Gene Therapies in Lung Cancer: Mechanisms of Local Delivery, Systemic Immune Effects, and Global Feasibility"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3338-8107","authenticated-orcid":false,"given":"Mihai","family":"Olteanu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine-Pneumology, Faculty of Medicine, University of Medicine and Pharmacy from Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Marina","family":"Andrei","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Pneumology, Faculty of Medicine, University of Medicine and Pharmacy from Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6335-1627","authenticated-orcid":false,"given":"Ramona","family":"Cioboat\u0103","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Pneumology, Faculty of Medicine, University of Medicine and Pharmacy from Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-7583","authenticated-orcid":false,"given":"Virginia Maria","family":"R\u0103dulescu","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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