Deciphering the loop of epithelial-mesenchymal transition, inflammatory cytokines and cancer immunoediting

- Tumorigenesis and tumor progression depend on cell-cell interaction, cell-ECM interaction and soluble cues (i.e. cytokines, growth factors).
- Innate and adaptive immunity shapes tumor fate and the phenotypic plasticity is a common feature of epithelial and immune cells.
- EMT is a physiological and coordinated program in which epithelial cells acquire motile phenotype and the characteristics of mesenchymal cells.
- In tumors EMT is a leading process regulating cancer invasion, cell phenotypic heterogeneity, stemness, immune escape and resistance to therapy.
- EMT is induced by the cooperation of signaling pathways activated by the dialogue between tumor cells and stromal cells in an inflammatory TME.

Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness. In this review we will outline how the dysregulation of microenvironmental signaling is crucial in determining tumor plasticity and EMT, arguing how therapy resistance hinges on these dynamics.

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