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FRIMEDBIO-Fri med.,helse,biol

Deciphering the molecular and functional heterogeneity of group 2 innate lymphoid cells in cancer.

Alternative title: Heterogeneity of group 2 innate lymphoid cells in cancer

Awarded: NOK 3.9 mill.

Cancer immunotherapy is the form of cancer treatment that has witnessed the most exciting advances in the field. The key to the successful immunotherapy is an improved understanding of the interactions between the components of the immune system and cancer cells. The aim of our project is to advance our understanding of the role of group 2 innate lymphoid cells (ILC2s) in cancer. ILC2s represent the most recently identified member of the innate lymphoid cell (ILC) family and serve as the first line of defence to fight infections and maintain tissue integrity. However, the nature of their interactions with cancer cells has only recently begun to be unveiled. In our project, we focus on ILC2s and investigate the mechanisms that regulate their function in the complex tumor microenvironment. So far, we have managed to identify specific components of the innate immune system that closely interact with ILC2s in the tumor microenvironment and either enhance their tumor suppressing activity or contribute to the tumor growth and progression. We will now focus on the possibility to enhance the tumor suppressing activity of ILC2s using therapeutic agents such as monoclonal antibodies as well as specific genetically engineered mouse models. We believe that our results might contribute to the development of new cancer immunotherapies in the future.

Cancer is associated with a heavy burden on society in terms of health and economic costs. Although great advances have occurred in the field of cancer immunotherapy, the benefit, to date, has been limited to a minority of patients with certain cancer types. In addition, as a result of more successful immunotherapy treatments, a significant subset of patients who initially respond but eventually relapse emerged. Group 2 innate lymphoid cells (ILC2s) represent the most recently identified member of the innate lymphoid cell (ILC) family. Their role in cancer seems contradictory, as they have been associated with tumor-suppressing as well as tumor-promoting activities. Therefore, the possibility to enhance and/or reorientate their tumor-suppressing and/or tumor-promoting activities, respectively, provides an attractive strategy in the field of cancer immunotherapy. This therapeutic strategy requires, however, a better understanding of the role and the mechanisms that regulate the function of ILC2s in different tumor sites, when facing complex interactions with the cellular and molecular components of the tumor microenvironment. Our preliminary data and the literature strongly support the hypothesis that the immune microenvironment is highly variable between different tumors or even areas of the same tumor. In addition, recent evidence indicates that metabolic pathways within the tumor microenvironment shape the diversity of infiltrating immune cells. Therefore, the current proposal aims to characterize ILC2s in different tumor areas and their contribution to the tumor growth as well as to assess the impact of tumor-derived lactic acid on the function of intratumoral ILC2s. A broader understanding of the relevance of ILC2s in cancer is essential towards the design of safe and successful therapeutic strategies.

Funding scheme:

FRIMEDBIO-Fri med.,helse,biol