Permissive State of EMT: The Role of Immune Cell Compartment

Abstract

The Epithelial to Mesenchymal Transition (EMT) type 3 is a reversible dynamic process recognized as a major determinant of the metastatic event, although many questions regarding its role throughout this process remain unanswered. The ability of cancer cells to migrate and colonize distant organs is a key aspect of tumor progression and evolution, requiring constant tumor cells and tumor microenvironment (TME) changes, as well as constant changes affecting the cross-talk between the two aforementioned compartments. Alterations affecting tumor cells, such as transcription factors, trans-membrane receptors, chromatin remodeling complexes and metabolic pathways, leading to the disappearance of the epithelial phenotype and concomitant gaining of the undifferentiated mesenchymal phenotype are undoubtedly major players of the EMT process. However, several lines of evidence point out toward a more critical role of TME composition in creating an "EMT-permissive state." The "EMT-permissive state" consists in changes affecting physical and biochemical properties (i.e., stiffness and/or hypoxia) as well as changes of the TME cellular component (i.e., immune-cell, blood vessel, lymphatic vessels, fibroblasts, and fat cells) that favor and induce the epithelial mesenchymal transition. In this mini review, we will discuss the role of the tumor microenvironment cellular component that are involved in supporting the EMT, with particular emphasis on the immune-inflammatory cells component.

Flow cytometry detection of cell type-specific expression of programmed death receptor ligand-1 (PD-L1) in colorectal cancer specimens

“…PD-L1 expression on tumor cells and antigen-presenting cells (APCs) is strongly upregulated by cytokines secreted by activated immune cells, such as IFN-γ or IL-1α [25,26]. Several lines of evidence have indicated that stromal cells and immune infiltrates can efficiently promote the EMT process in a paracrine manner [34,35,36]. This suggests that those non-malignant cells in the TME may contribute to the induction of PD-L1 expression together with EMT on tumor cells.…”

Intratumoural administration and tumour tissue targeting of cancer immunotherapies

“…TGFβ is a crucial cytokine involved in promoting epithelial–mesenchymal transition and the induction of immunosuppressive T reg cells, which support tumour progression 233 . In situ targeting of TGFβ has been made possible with the development of bintrafusp alfa, a fusion of a tumour-targeted anti-PD-L1 antibody (avelumab) with a TGFβ-receptor trap.…”

Cancer drug resistance induced by EMT: novel therapeutic strategies

“…Tumour promoting and tumour suppressive immunocytes and inflammatory cells as well as their molecular products are abundantly present in the TME (Maman and Witz 2018). The inflammatory cells as well as their secretome have the capacity to induce, drive and maintain EMT (Yan et al 2018;Fedele and Melisi 2020). Tumour-associated macrophages (TAMs) are the largest non-tumour cell population in the TME.…”