We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.
- Authors
Vahl, Julius Malte; Friedrich, Juliane; Mittler, Susanne; Trump, Sonja; Heim, Lisanne; Kachler, Katerina; Balabko, Liubov; Fuhrich, Nicole; Geppert, Carol-Immanuel; Trufa, Denis Iulian; Sopel, Nina; Rieker, Ralf; Sirbu, Horia; Finotto, Susetta
- Abstract
<bold>Background: </bold>Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.<bold>Methods: </bold>Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer.<bold>Results: </bold>Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis.<bold>Conclusions: </bold>These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.
- Publication
British Journal of Cancer, 2017, Vol 117, Issue 8, pN.PAG
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2017.336