RESEARCH SUMMARY

Inflammation is a complex stereotypical response that is essential for effective defence of the organism against harmful stimuli such as pathogens, irritants or tissue damage. Discovery of the detailed processes of inflammation has revealed a close relationship between the inflammatory reaction and the immune response. Indeed, a hallmark of inflammation is the directed migration (chemotaxis) of inflammatory cells (mostly leukocytes) through blood vessel walls to the site of injury. Once wound healing is complete, inflammation resolves and tissue homeostasis returns. Nonetheless, a deregulated response to tissue damage might lead to autoimmunity and chronic inflammatory diseases, and can also promote cancer.

Recent clinical and experimental evidence indicates that solid tumours exacerbate inflammation to promote their own progression. This leads to a tumour microenvironment largely orchestrated by inflammatory cells, altering the metabolic needs of the tissue and fostering neoangiogenesis, proliferation, survival, mutagenesis, migration and metastasis of malignant cells.

Tumour-induced inflammation usually leads to immunosuppression, impeding the immune system surveillance function and clearance of the tumour; indeed, breaking immunosuppression has been demonstrated as a useful, efficient way to eradicate cancers. Immune cells might therefore provide both anti- and protumourigenic signals, which could be harnessed or attacked for therapeutic purposes. We aim to identify and understand key molecules/pathways responsible for the aberrant inflammatory reaction involved in the development or outcome of inflammation-associated pathologies.

Our research projects focus on distinct steps of this reaction:

(i) Study at the cellular level of key signalling pathways that regulate acquisition of a motile phenotype in leukocytes

(ii) Understand the role of specific chemokines/chemokine receptors in orchestrating the activation of the adaptive immune response

(iii) Identify key regulators of terminal differentiation in innate immune cells within the inflammatory environment

(iv) Examine the relevance of the vascular system in controlling inflammatory migration of specific leukocyte subtypes

We hope to understand critical cellular, molecular, and chemical mediators through which tumours promote inflammation and subvert the immune system to favour their progression. Comprehension of the mechanisms that balance pro- and anti-tumour immunity could lead to the design of more effective anti-cancer therapeutics. Although the major focus of our research is the inflammatory reaction to cancer, we are also interested in understanding the chronic inflammation associated to autoimmune diseases.