title: Mast cell phenotype, TNFα expression and degranulation status in non-small cell lung cancer.
abstract: Mast cell infiltration of tumour islets represents a survival advantage in non-small cell lung cancer (NSCLC). The phenotype and activation status of these mast cells is unknown. We investigated the mast cell phenotype in terms of protease content (tryptase-only [MCT], tryptase + chymase [MCTC]) and tumour necrosis factor-alpha (TNFα) expression, and extent of degranulation, in NSCLC tumour stroma and islets. Surgically resected tumours from 24 patients with extended survival (ES; mean survival 86.5 months) were compared with 25 patients with poor survival (PS; mean survival 8.0 months) by immunohistochemistry. Both MCTand MCTCin tumour islets were higher in ES (20.0 and 5.6 cells/mm2respectively) compared to PS patients (0.0 cells/mm2) (p < 0.0001). Both phenotypes expressed TNFα in the islets and stroma. In ES 44% of MCTand 37% of MCTCexpressed TNFα in the tumour islets. MCTin the ES stroma were more degranulated than in those with PS (median degranulation index = 2.24 versus 1.73 respectively) (p = 0.0022), and ES islet mast cells (2.24 compared to 1.71, p < 0.0001). Since both MCTand MCTCinfiltrating tumour islets in ES NSCLC patients express TNFα, the cytotoxic activity of this cytokine may confer improved survival in these patients. Manipulating mast cell microlocalisation and functional responses in NSCLC may offer a novel approach to the treatment of this disease.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Shikotra
authors.affiliation: University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Ohri
authors.affiliation: University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
authors.forename: R H
authors.initials: RH
authors.lastname: Green
authors.affiliation: University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Waller
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bradding
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D015550:Cell Degranulation; D002465:Cell Movement; D053818:Chymases / Q000235:genetics* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D010641:Phenotype; D016019:Survival Analysis; D053802:Tryptases / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D053818:Chymases; D053802:Tryptases