Role of Interleukin-22 in immune escape and metastasis

Principal Investigators

Scientific Staff

Dr. rer. nat. Daria Briukhovetska – Postdoc

Project Description

Cancer is intimately linked to the immune system in control, development and also progression. Nowadays, the impact of immunity on cancer control is well established and has led to major breakthroughs in medicine with the implementation of T cells as therapeutic target structures, with the potential to cure even advanced disease. A less known and understood phenomenon is the role of T cells in disease progression. While immune suppressive T cells are well established, their function is quite equivocal with regards to cancer. Along these lines, impact on disease might rather stem from functional and phenotypic heterogeneity rather than a one fits all phenomenon. We and others could previously demonstrate that T cells, especially CD4+ T cells are quite diverse in their profile in cancer patients and models. There T cells producing the cytokine IL-22 appear to be of particular interest. A vast body of literature has demonstrated the prognostic value of IL-22 producing T cells across disease entity but the reason for a correlation with a dismal outcome is poorly understood. We could previously demonstrate that cancer cells specifically regulate IL-22 production from memory CD4+ T cells. In unpublished work, we went on to demonstrate that IL-22 is critically required for metastasis to the lung and other organs. We found that CD4+ T cells are the major source of this prometastatic function which functions through signaling via the IL-22-receptor on circulating cancer cells. We now aim at deciphering the mechanisms of this immune controlled metastasis axis.

Aims

(I) Understand the impact of IL-22 signaling on cancer cells to drive metastasis

(II) Understand the functional consequences of IL-22 on immune function

(III) Explore avenues of therapeutic intervention

Publications

1. Kobold S, Kobold S, Völk S, Clauditz T, Küpper NJ, Minner S, Tufmann A, Düwell P, Lindner M, Koch I, Heidegger S, Rothenfußer S, Schnurr M, Huber R, Wilczak W and Endres S: Interleukin-22 is frequently expressed in lung cancer and may contribute to tumor progression in chemotherapy-resistant disease.Journal of Thoracic Oncology, 2013; 8(8): 1032-42 S, Clauditz T, Küpper NJ, Minner S, Tufmann A, Düwell P, Lindner M, Koch I, Heidegger S, Rothenfußer S, Schnurr M, Huber R, Wilczak W and Endres S:
2. Voigt C, May P, Gottschlich A, Markota A, Wenk D, Gerlach I, Voigt S, Stathopoulos GT, Arendt KAM, Heise C, Rataj F, Janssen KP, Königshoff M, Winter H, Himsl I, Thasler WE, Schnurr M, Rothenfußer S, Endres S, Kobold S: Cancer cells induce interleukin-22 production from memory CD4+ T cells via interleukin-1 to promote tumor growth. Proc Natl Acad Sci USA 2017, 114:12994-12999.