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 MCT and MCTC 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 MCT and 37% of MCTC expressed TNFα in the tumour islets. MCT 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 MCT and MCTC 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.
Highlights
Mast cells exhibit marked heterogeneity across species, within different organs within the same species, and even within the same organ[5]
This study extends those findings by delineating the phenotype of mast cells within the tumour stroma and epithelial islets, and the extent of their degranulation
Both protease phenotypes are present within the tumour islets of patients with extended survival (ES), they express TNFα, and the presence of both is associated with increased survival following surgical resection
Summary
Mast cells exhibit marked heterogeneity across species, within different organs within the same species, and even within the same organ[5]. MCT predominate in mucosal epithelia, and are present in the lamina propria[18,19] Their roles remain unclear, but their ability to release different proteases and cytokines[18,19] suggests some roles which are mutually exclusive. We have shown previously that increased expression of TNFαin the tumour islets of patients with NSCLC is independently associated with improved survival[25]. Whether the MCTC mast cell phenotype infiltrates the tumour islets, expresses TNFα, and confers a survival advantage has not been reported. The primary aims of the present study were to define the phenotype of mast cells within NSCLC stroma and islets in terms of their protease and TNFαcontent and their state of activation defined by the extent of degranulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
