{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T21:39:47Z","timestamp":1763415587938,"version":"3.41.2"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005722","name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Internal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Levels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.858212","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T16:37:53Z","timestamp":1656347873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Markers of Immune Cell Exhaustion as Predictor of Survival in Surgically-Treated Early-Stage NSCLC"],"prefix":"10.3389","volume":"13","author":[{"given":"Laura","family":"Sellmer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Kov\u00e1cs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Kumbrink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Kauffmann-Guerrero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemarie","family":"Kiefl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Behr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Tufman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer Statistics 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA: A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2010.11.008","article-title":"Randomized Trial of Mediastinal Lymph Node Sampling Versus Complete Lymphadenectomy During Pulmonary Resection in the Patient With N0 or N1 (Less Than Hilar) non-Small Cell Carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial","volume":"141","author":"Darling","year":"2011","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3182862e7e","article-title":"Influence of Postoperative Infectious Complications on Long-Term Survival of Lung Cancer Patients: A Population-Based Cohort Study","volume":"8","author":"Andalib","year":"2013","journal-title":"J Thorac Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000002886","article-title":"Perioperative Management may Improve Long-Term Survival in Patients After Lung Cancer Surgery: A Retrospective Cohort Study","volume":"126","author":"Huang","year":"2018","journal-title":"Anesth Analgesia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(20)30002-9","article-title":"CT Derived Radiomic Score for Predicting the Added Benefit of Adjuvant Chemotherapy Following Surgery in Stage I, II Resectable non-Small Cell Lung Cancer: A Retrospective Multicohort Study for Outcome Prediction","volume":"2","author":"Vaidya","year":"2020","journal-title":"Lancet Digital Health"},{"key":"B6","doi-asserted-by":"publisher","first-page":"6869","DOI":"10.2147\/CMAR.S186047","article-title":"The Number of Resected Lymph Nodes is Associated With the Long-Term Survival Outcome in Patients With T2 N0 non-Small Cell Lung Cancer","volume":"10","author":"Wen","year":"2018","journal-title":"Cancer Manage Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.3389\/fimmu.2018.02810","article-title":"Tissue Resident CD8 Memory T Cell Responses in Cancer and Autoimmunity. 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