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Doctoral thesis

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Cross-talk between macrophages and tumour cells during tissue homeostasis in Drosophila Melanogaster

Tissue homeostasis

Doctoral student: Inés Kelleher

Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid

Thesis adviser:

Inés Kelleher

Sinopsis

The innate immune system plays a key role in the response to pathogens, tissue damage and tumoral progression. Tumors are a heterogeneous mass of abnormal cells which contain and interact with cells from the innate immune system, such as tumor associated macrophages otherwise known as TAMs. These TAMs can have opposing functions during cancer progression as they can both promote or restrict tumor growth depending on the tumoral stage and various signaling processes during tumoral development. This functional plasticity of TAMs as well as their interactions with the tumor are an area of great interest as they can be exploited and manipulated for the development of new anticancer therapies.

To study the interaction of TAMs with the tumoral tissue we will use a tumor model generated in Drosophila melanogaster which recruits innate immune blood cells that present similar functions to vertebrate macrophages. The innate immune system of insects is formed by hemocytes which perform functions such as phagocytosis, tissue remodeling and protection against external infections. In the context of tumor formation, we have demonstrated that hemocytes are recruited in great number to the tissue which will allow us to use a simple and genetic tractable model to decipher the role of macrophages during tumor formation and progression.

Our main objective is to study the intricate molecular cross-talk between hemocytes and tumor cells as well as the role of hemocytes during tumor formation. To this end, we will use state-of-the-art genetic, molecular and genome wide technologies to describe the plasticity of TAMs and manipulate gene expression either in tumor cells or hemocytes. With these results we aim to shed light on the functional plasticity of tumor associated macrophages and its impact on tumor development. As the relationship between TAMs and tumors becomes clearer, TAMs will become a promising target for developing new cancer treatments.

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