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Eur Respir J. 2015 Dec;46(6):1762-72. doi: 10.1183/13993003.00176-2014. Epub 2015 Nov 5.

Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer.

Author information

1
Department of Respiratory Medicine, Mater Misericordiae University Hospital, Dublin, Ireland Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland Both authors contributed equally.
2
UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland Both authors contributed equally.
3
Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland.
4
Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland Mid-Western Cancer Centre, University Hospitals, Limerick, Ireland.
5
LABMED Directorate, St James's Hospital, Dublin, Ireland.
6
Molecular Oncology Laboratory, Royal College of Surgeons in Ireland, Dublin, Ireland.
7
UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
8
Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Australia kenneth.o'byrne@health.qld.gov.au.

Abstract

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8(+) TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3(+) TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8(+) islet (HR 0.48, p<0.001) and Foxp3(+) stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3(+) and CD8(+) stromal counts and high Foxp3(+) islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8(+) TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3(+) TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.

PMID:
26541534
DOI:
10.1183/13993003.00176-2014
[Indexed for MEDLINE]
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