Phd in IINNOVATION IN IMMUNO-MEDIATED AND HEMATOLOGICAL DISORDERS

Thesis title: Unveiling mast cell plasticity in colorectal cancer

Mast cells (MCs) are tissue-resident cells derived from hematopoietic lineage. MC progenitors (MCps) enter the circulation and mature in peripheral tissues under local microenvironmental factors. MCs are predominantly located at sites of interaction with the external environment and around blood vessels. They play an important role in the body's immune system, particularly in allergic reactions and are also implicated in various health and disease conditions, playing an important role in the different stages of tumor development. MCs play either a pro- or anti-tumoral activity, depending on the microenvironment in which they reside. Using a murine model of colitis-induced colon cancer, we have highlighted the phenotypic and functional heterogeneity of mast cells during cancer progression. We identified distinct clusters of mast cells that differ in their maturation states, phenotypes, and functional roles, highlighting the dynamic plasticity of these cells in pathological contexts. We found that SCF and IL-33 in the tumor microenvironment drive MCs toward a pro-inflammatory phenotype, facilitating tumor progression through cytokine production. Future studies are needed to explore the regulatory mechanisms controlling MC differentiation within tumors and investigate how these cells interact with other components of the immune system in the context of CRC.