Mast cell phenotype, TNFα expression and degranulation status in non-small cell lung cancer

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 [MC_T], tryptase + chymase [MC_TC]) 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 MC_T and MC_TC in tumour islets were higher in ES (20.0 and 5.6 cells/mm² respectively) compared to PS patients (0.0 cells/mm²) (p < 0.0001). Both phenotypes expressed TNFα in the islets and stroma. In ES 44% of MC_T and 37% of MC_TC expressed TNFα in the tumour islets. MC_T in 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 MC_T and MC_TC infiltrating 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.