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ERC

REGiREG Report Summary

Project ID: 648145
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - REGiREG (Regulating the immune regulators: targeting adaptive immune control)

Reporting period: 2015-07-01 to 2016-12-31

Summary of the context and overall objectives of the project

The immune system with its complex interactions of cells and molecules needs a very tight and specific interplay of control elements to ensure the establishment and re-establishment of immune homeostasis after challenges. Regulatory T cells are key-players in this regulatory network. It is now well accepted that deficiency or dysfunction of regulatory T cells causes various severe immune disorders due to immune hyperactivation. Conversely, an increased number of regulatory T cells in tumor-bearing individuals suppresses efficient anti-tumor immunity and, thereby, is often associated with poor prognosis. Cancer immunology is now one of the most exciting and promising frontiers in cancer research, and recent clinical trials have proven that immunotherapies driving to activate T cells can induce durable responses. In this sense, harnessing the potential of regulatory T cells is one of the most promising new approaches to control immune function and to treat cancer. This proposal has two objectives: 1, the identification and characterization of tissue-resident regulatory T cells to principally understand the unique features of regulatory T cell specialization in tissues and their function in organ-homeostasis, a phenomenon that is hardly understood, but holds great promise for local, tissue-specific immune intervention. 2, to globally target regulatory T cells, including the lymphoid organ regulatory T cell pool, by interfering with their survival and or suppression function. We expect from these studies new basic insights into a fascinating and still arcane aspect of organ-homeostasis as maintained by regulatory T cells, as well as novel inhibitors and candidate molecules that target regulatory T cells at the systemic level, and eventually at a tissue-specific level.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Within the first 18 month of the project, we were able to establish several novel tools and technologies to study regulatory T cells. We established new in vivo model systems and in vitro test systems. We started to characterize regulatory T cells on a molecular level from different tissues and their function.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We implemented a novel technology to analyze the DNA methylation status of very few cells. With this whole-genome bisulfite sequencing technology, we were able to study the epigenetic changes of DNA methylation of regulatory T cells. Analyzing the epigenetic landscape is more than a complementary approach to describe regulatory T cells; it will help to define identities of regulatory T cell subgroups and the permanent underlying molecular programs. These programs can then be potential targets for novel therapies.
Record Number: 198123 / Last updated on: 2017-05-17