title: Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer.
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.
authors.affiliation: Department of Respiratory Medicine, Mater Misericordiae University Hospital, Dublin, Ireland Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland Both authors contributed equally.
authors.forename: Dermot S
authors.initials: DS
authors.lastname: O'Callaghan
authors.affiliation: UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland Both authors contributed equally.
authors.forename: Elton
authors.initials: E
authors.lastname: Rexhepaj
authors.affiliation: Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland.
authors.forename: Kathy
authors.initials: K
authors.lastname: Gately
authors.affiliation: Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland Mid-Western Cancer Centre, University Hospitals, Limerick, Ireland.
authors.forename: Linda
authors.initials: L
authors.lastname: Coate
authors.affiliation: LABMED Directorate, St James's Hospital, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Delaney
authors.affiliation: Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland.
authors.forename: Dearbhaile M
authors.initials: DM
authors.lastname: O'Donnell
authors.affiliation: Molecular Oncology Laboratory, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Kay
authors.affiliation: Thoracic Oncology Research Group, Trinity College Dublin, Dublin, Ireland.
authors.forename: Finbarr
authors.initials: F
authors.lastname: O'Connell
authors.affiliation: UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.affiliation: 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.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011013:Pneumonectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)