Understanding the Role of Cytokines in the Onset and Progression of Intestinal-Type Gastric Cancer — ASN Events

Understanding the Role of Cytokines in the Onset and Progression of Intestinal-Type Gastric Cancer (#306)

Paul Nguyen 1 2 , Rita Busuttil 3 , Lisa Mielke 1 2 , Gabrielle Belz 1 2 , Alex Boussioutas 3 , Matthias Ernst 1 2 , Tracy Putoczki 1 2
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, Melbourne University, Parkville, VIC, Australia
  3. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Gastric cancer (GC) is the fourth most prevalent cancer worldwide, and the third most common cause of cancer-related death. The disease is generally asymptomatic and as a result is often diagnosed at an advanced stage, at which point metastasis is present in greater than 80% of patients. Treatment options for GC are limited; however, current therapeutic strategies have embraced the concept of targeting components of the inflammatory microenvironment. In light of this, we aimed to characterise the role of cytokines produced by mucosal immune cell populations during onset and progression of intestinal-type gastric cancer (IGC). We compared microarray data from a panel of >40 human IGC biopsies and adjacent non-tumour tissue to characterise the expression of cytokines and transcription factors classically associated with chronic inflammation. Since we could detect numerous pro-inflammatory cytokines in human IGC tumour tissue, we characterised the role of individual cytokines in disease progression using a validated mouse model of IGC, referred to as gp130Y757F (1). We found that genetic restriction of IL-10 and IL-12 (p40) in did not alter disease progression in gp130Y757F mice. Meanwhile, loss of IL-6, IL-17A and IL-23 (p19) expression delayed gastritis, but did not alter the progression of established gastric adenomas. In contrast, genetic inhibition of IL-18, or therapeutic inhibition of IL-22 significantly reduced gastric tumour burden. Our results suggest stage-specific roles for various cytokines during IGC progression, and identify IL-18 and IL-22 as potential therapeutic targets for this disease.

  1. Cancer Cell. (2013). 24(2): 257