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 differentiate under microenvironmental factors present at target tissues. 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 different tumors. MCs play either a pro- or anti-tumoral activity, depending on the microenvironment in which they reside. In this study, we have demonstrated the phenotypic and functional heterogeneity of mast cells in colorectal cancer using a murine model of colitis-induced colon cancer. We identified distinct clusters of mast cells that differ in their maturation states, phenotypes, and functional roles in the tumor microenvironment, highlighting the dynamic plasticity of these cells in pathological contexts. We found that SCF and IL-33 in the TME drive MCs toward a pro-inflammatory phenotype, facilitating tumor progression through cytokine and chemokine 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.