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Clin Cancer Res. 2015 Jun 1;21(11):2635-43. doi: 10.1158/1078-0432.CCR-14-1905. Epub 2015 Feb 13.

Stromal CD8+ T-cell Density—A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer.

Author information

1
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.
2
Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway.
3
Department of Oncology, University Hospital of North Norway, Tromso, Norway. Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway.
4
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway.
5
Department of Oncology, University Hospital of North Norway, Tromso, Norway.
6
Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
7
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
8
Department of Oncology, Rigshospitalet, Copenhagen, Denmark. Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
9
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Department of Pathology, Odense University Hospital, Odense, Denmark.
10
Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
11
Department of Oncology, Odense University Hospital, Odense, Denmark. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
12
Department of Pathology, Nordland Hospital, Bodo, Norway.
13
Institute of Medical Biology, The Arctic University of Norway, Tromso, Norway. Department of Pharmacy, The Arctic University of Tromso, Tromso, Norway.
14
Department of Community Medicine, The Artic University of Tromso, Tromso, Norway.
15
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract

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.

PMID:
25680376
DOI:
10.1158/1078-0432.CCR-14-1905
[Indexed for MEDLINE]
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