IL-6 Promotes TNFR2-expressing Tregs

Lead researcher

Dr Nirmala Chandralega-Kampan

Main finding

Interleukin-6 (IL-6) in ascites fluid can increase the proportion of TNFR2+ T-regulatory cells (Tregs), to inhibit the activity of anti-tumour T-effector cells (Teffs) and promote immune suppression. Blockade of IL-6 signalling decreased immune suppression, decreased the expression of several checkpoint inhibitor molecules, and increased Teff activity.

Centre

Centre for Cancer Research

Research group

Ovarian Cancer Biomarkers

Co-authors

Dr Mutsa Tatenda Madondo
A/Prof Orla M. McNally
Dr Andrew N. Stephens
Prof Michael A. Quinn
Prof Magdalena Plebanski

Journal and article title

Frontiers in Immunology

Interleukin 6 present in inflammatory ascites from advanced epithelial ovarian cancer patients promotes tumour necrosis factor receptor 2-expressing regulatory T cells

Most surprising

Immune-suppressive TNFR2+ Tregs can arise de novo through the influence of IL6, rather than migrating into the tumour environment as previously hypothesized. These TNFR2+ Tregs have potent immunosuppressive activity, and inhibit TNFR2+ T effector cells to enhance immune suppression in ovarian cancers.

Future implications

The use of therapies to antagonize IL-6 signalling can stimulate anti-tumour immunity through a reduction in Treg abundance, whilst simultaneously increasing T effector cell function. This could lead to novel adjunct therapies for patients.

Disease/health impact

ovarian cancer