Tumor Immune Microenvironment during Epithelial–Mesenchymal Transition

Abstract

Epithelial-mesenchymal transition (EMT) has been shown to play a critical role in tumor development from initiation to metastasis. EMT could be regarded as a continuum, with intermediate hybrid epithelial and mesenchymal phenotypes having high plasticity. Classical EMT is characterized by the phenotype change of epithelial cells to cells with mesenchymal properties, but EMT is also associated with multiple other molecular processes, including tumor immune evasion. Some previous studies have shown that EMT is associated with the cell number of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), and the expression of immune checkpoints, such as programmed cell death-ligand 1, in several cancer types. At the molecular level, EMT transcriptional factors, including Snail, Zeb1, and Twist1, produce or attract immunosuppressive cells or promote the expression of immunosuppressive checkpoint molecules via chemokine production, leading to a tumor immunosuppressive microenvironment. In turn, immunosuppressive factors induce EMT in tumor cells. This feedback loop between EMT and immunosuppression promotes tumor progression. For therapy directly targeting EMT has been challenging, the elucidation of the interactive regulation of EMT and immunosuppression is desirable for developing new therapeutic approaches in cancer. The combination of immune checkpoint inhibitors (ICIs) and immunotherapy targeting immunosuppressive cells could be a promising therapy for EMT.Research.

PLEK2 promotes osteosarcoma tumorigenesis and metastasis by activating the PI3K/AKT signaling pathway

“…The EMT process is closely associated with cancer progression and metastasis. The molecular changes that occur in epithelial cancer cells are characteristic of EMT, including the acquisition of mesenchymal qualities and the loss of epithelial features ( 7 , 23 ). These primary features enhance cancer cell migration and invasion, and increase antitumoral therapy resistance ( 32 ).…”

“…Tumor metastasis is associated with the tumor microenvironment, which plays a key role in the progression of malignant tumors ( 6 ). The epithelial-to-mesenchymal transition (EMT) process is a crucial mechanism in the progression of tumor metastasis and is characterized by the loss of cell-cell adhesions and the acquisition of cell-matrix interactions ( 7 ). EMT is involved in the formation of several tissues and organs during embryonic development, in addition to tumor invasion and metastases ( 8 ).…”

Partial EMT in Squamous Cell Carcinoma: A Snapshot

“…These results indicate that the pEMT phenotype cells may be the most suitable for metastasis. The feedback loop between EMT and immunosuppression promotes tumor progression 22 , 23 , but how pEMT affects tumor immunity remains undiscussed 24 .…”

A Panel of Emerging EMT Genes Identified in Malignant Mesothelioma

“…The immunosuppressive cells in turn promote EMT in tumor cells. The interaction between EMT and immunosuppression promotes tumor progression 41 . Tumor-infiltrating immune cells release a wide variety of inflammatory mediators and growth factors to facilitate immunosuppressive microenvironment and EMT plasticity.…”