CANBIO II – Training in Cancer Biology 2: Focus on the Tumor Ecosystem

The project at a glance

Start date:

04 Jan 2022
Duration in months:

72
Funding:

FNR – Luxembourg
Principal Investigator(s):

Iris BEHRMANN

Stephanie KREIS

Elisabeth LETELLIER

Simone Niclou (external)

Barbara Klink (external)

Johannes Meiser (external)

About

Building on our successful first Doctoral Training Unit in Cancer Biology (CANBIO) within the first FNR PRIDE program, we are keen to continue to provide state-of-the-art training for doctoral candidates in cancer research in Luxembourg. This proposal takes advantage of the network and expertise generated in CANBIO1, while incorporating novel scientific insight and addressing pertinent questions in the cancer field. In CANBIO1 our research focused on tumor escape mechanisms, investigating key aspects of intrinsic and induced escape mechanisms in response to therapy. The present application aims to generate new insight into the tumor ecosystem (TE) and to harness this knowledge for improved treatment options. Over the years, cancer research has moved from a tumor-centric view to an organ-type view of cancer recognizing the importance of the tumor microenvironment (TME) in tumor growth and progression. The clinical relevance of the TME is highlighted by the observation that pre-existing immune parameters correlate with patient survival, exemplified by the emergence of the immunoscore for the classification of gastrointestinal cancer. However beyond the immediate TME which includes stromal cells, infiltrating immune cells, extracellular matrix, available nutrients and secreted factors, cancer development and metastatic growth are also under distant organismal influences such as systemic immunity, the gut microbiome and metabolic conditions. Newly described forms of communication e.g. through extracellular vesicles have been recognized as important components of cellular interactions in the local TME and systemic circulation. In the context of immunotherapy there is growing appreciation that immune cell manipulation and recruitment need to be considered beyond the tumor site. For example, glioblastoma (GBM), a deadly brain cancer, is not only characterized by a highly immunosuppressive TME, but also displays systemic immune suppression, including immune cell dysfunction and T cell lymphopenia. Furthermore it is recognized that cancer metabolism is not limited to metabolic reprogramming of cancer cells, and increasing efforts aim to understand the metabolic interactions between cancer and non-neoplastic cells. Dietary interventions are studied to regulate nutrient availability at an organismal level and insight into the impact of the microbiome on cancer progression and treatment is gaining momentum. Such processes are of utmost importance in the context of metastasis, where colonization far away from the primary tumor relies on immunosuppressive and tumor supportive factors at a systemic level. Understanding the nature of these complex dialogues is at the center of this research program, which will allow for improved therapeutics that simultaneously target the cancer cell and multiple components of the TE. We value your feedback and inquiries. Contact prof. Iris Behrmann.

LIH – CANBIO2