PMID- 25680376 OWN - NLM STAT- MEDLINE DCOM- 20160222 LR - 20220321 IS - 1557-3265 (Electronic) IS - 1078-0432 (Linking) VI - 21 IP - 11 DP - 2015 Jun 1 TI - Stromal CD8+ T-cell Density-A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer. PG - 2635-43 LID - 10.1158/1078-0432.CCR-14-1905 [doi] AB - PURPOSE: Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates, which appears to be superior to the tumor-node-metastasis (TNM) classification in colorectal cancer. In non-small cell lung cancer (NSCLC), no immunoscore has been established, but in situ tumor immunology is recognized as highly important. We have previously evaluated the prognostic impact of several immunological markers in NSCLC, yielding the density of stromal CD8(+) tumor-infiltrating lymphocytes (TIL) as the most promising candidate. Hence, we validate the impact of stromal CD8(+) TIL density as an immunoscore in NSCLC. EXPERIMENTAL DESIGN: The prognostic impact of stromal CD8(+) TILs was evaluated in four different cohorts from Norway and Denmark consisting of 797 stage I-IIIA NSCLC patients. The Tromso cohort (n = 155) was used as training set, and the results were further validated in the cohorts from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts. RESULTS: Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P < 0.001), disease-specific survival (P < 0.001), or overall survival (P < 0.001). Subgroup analyses revealed significant prognostic impact of stromal CD8(+) TIL density within each pathologic stage (pStage). In multivariate analysis, stromal CD8(+) TIL density and pStage were independent prognostic variables. CONCLUSIONS: Stromal CD8(+) TIL density has independent prognostic impact in resected NSCLC, adds prognostic impact within each pStage, and is a good candidate marker for establishing a TNM-Immunoscore. CI - (c)2015 American Association for Cancer Research. FAU - Donnem, Tom AU - Donnem T AD - Department of Oncology, University Hospital of North Norway, Tromso, Norway. Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway. tom.donnem@uit.no. FAU - Hald, Sigurd M AU - Hald SM AD - Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway. FAU - Paulsen, Erna-Elise AU - Paulsen EE AD - Department of Oncology, University Hospital of North Norway, Tromso, Norway. Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway. FAU - Richardsen, Elin AU - Richardsen E AD - Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway. FAU - Al-Saad, Samer AU - Al-Saad S AD - Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway. FAU - Kilvaer, Thomas K AU - Kilvaer TK AD - Department of Oncology, University Hospital of North Norway, Tromso, Norway. FAU - Brustugun, Odd Terje AU - Brustugun OT AD - Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Helland, Aslaug AU - Helland A AD - Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Lund-Iversen, Marius AU - Lund-Iversen M AD - Institute of Clinical Medicine, University of Oslo, Oslo, Norway. FAU - Poehl, Mette AU - Poehl M AD - Department of Oncology, Rigshospitalet, Copenhagen, Denmark. Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Olsen, Karen Ege AU - Olsen KE AD - Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Department of Pathology, Odense University Hospital, Odense, Denmark. FAU - Ditzel, Henrik J AU - Ditzel HJ AD - Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. FAU - Hansen, Olfred AU - Hansen O AD - Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Al-Shibli, Khalid AU - Al-Shibli K AD - Department of Pathology, Nordland Hospital, Bodo, Norway. FAU - Kiselev, Yury AU - Kiselev Y AD - Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway. Department of Pharmacy, The Arctic University of Tromso, Tromso, Norway. FAU - Sandanger, Torkjel M AU - Sandanger TM AD - Department of Community Medicine, The Artic University of Tromso, Tromso, Norway. FAU - Andersen, Sigve AU - Andersen S AD - Department of Oncology, University Hospital of North Norway, Tromso, Norway. FAU - Pezzella, Francesco AU - Pezzella F AD - Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. FAU - Bremnes, Roy M AU - Bremnes RM AD - Department of Oncology, University Hospital of North Norway, Tromso, Norway. Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway. FAU - Busund, Lill-Tove AU - Busund LT AD - Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150213 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Biomarkers, Tumor) SB - IM MH - Aged MH - Biomarkers, Tumor/immunology MH - CD8-Positive T-Lymphocytes/*immunology/pathology MH - Carcinoma, Non-Small-Cell Lung/*immunology/pathology/surgery MH - *Cell Count MH - Disease-Free Survival MH - Female MH - Humans MH - Lymphocytes, Tumor-Infiltrating/*immunology/pathology MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Prognosis MH - Stromal Cells/*immunology/pathology EDAT- 2015/02/15 06:00 MHDA- 2016/02/24 06:00 CRDT- 2015/02/15 06:00 PHST- 2014/07/25 00:00 [received] PHST- 2015/02/01 00:00 [accepted] PHST- 2015/02/15 06:00 [entrez] PHST- 2015/02/15 06:00 [pubmed] PHST- 2016/02/24 06:00 [medline] AID - 1078-0432.CCR-14-1905 [pii] AID - 10.1158/1078-0432.CCR-14-1905 [doi] PST - ppublish SO - Clin Cancer Res. 2015 Jun 1;21(11):2635-43. doi: 10.1158/1078-0432.CCR-14-1905. Epub 2015 Feb 13.