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Spotlight Seminar - Ines Sequiera : The role of Keratins in modulating carcinogenesis via communication with cells of the immune system

When Nov 26, 2018
from 12:30 PM to 01:30 PM
Where Biffen lecture Theatre, underneath Dept of Genetics
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Spotlight Seminar:
Inês Sequeira will give a spotlight seminar at 12:30 on Monday 26th in the Biffen.

Title: The role of Keratins in modulating carcinogenesis via communication with cells of the immune system

Abstract: The inability to resolve chronic inflammation is considered one of the initial triggers of carcinogenesis. Until recently, keratins were mainly regarded as cytoskeletal scaffolds; however, there is an emerging role for keratins in the regulation of epidermal immunity. Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76-/- Tregs have increased suppressive ability correlated with increased CD39 and CD73 expression.

The Krt76-/- mouse serves as a model to explore the link between chronic inflammation and cancer, providing an opportunity to examine the impact of aberrant epithelial differentiation and consequent chronic inflammation on tumourigenesis. We observed that loss of Krt76 increases carcinogen-induced tumours in tongue and squamous stomach. The carcinogenesis response includes upregulation of pro-inflammatory cytokines and enhanced accumulation of Tregs in the tumour microenvironment.

Our study highlights the importance of keratins as immunomodulators and demonstrate their importance in tumour progression.