The Epithelial-to-Mesenchymal Transition (EMT) is a cell-biological process that operates during embryonic development, wound-healing, and carcinoma progression and facilitates the conversion of epithelial cells to more-mesenchymal derivatives. During this process, cells typically shed the expression of epithelial markers, such as E-Cadherin, and express instead, mesenchymal markers, such as vimentin, fibronectin and certain master EMT-inducing transcription factors (EMT-TFs), notably Zeb1, Twist, Snail and Slug; once expressed, these EMT-TFs regulate the expression of genes associated with the more-mesenchymal state of carcinoma cells. The EMT program is a highly dynamic process that often gives rise to a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal polarization spectrum. Importantly, mesenchymal cells can also lapse back into a more-epithelial state by the reverse process of mesenchymal-to-epithelial transition (MET).
Carcinoma cells that activate the EMT program acquire certain properties such as enhanced invasiveness and motility, enhanced metastatic potential, the gain of tumor-initiating or cancer stem-cell like properties and refractory responses to multiple cytotoxic therapies. Importantly, there is also beginning to emerge a growing appreciation of the ability of mesenchymal carcinoma cells to modulate the tumor microenvironment and drive refractory responses to multiple immunotherapies, including immune checkpoint blockade. In addition to the contextual signals operating within the confines of the primary tumor microenvironment, various immune cells also regulate distinct steps of the metastatic cascade and are functionally important in the formation of the pre-metastatic niche at distant organ sites. The details of the mechanistic maneuvers utilized by carcinoma cells undergoing an EMT to actively evade and suppress anti-tumor immunity opens a new avenue of investigation - one that may likely provide a unique opportunity to sensitize highly refractory mesenchymal cells to immune attack by identifying novel therapeutic targets. An additional unexplored avenue is the generalizability of the EMT program to modulate the immune response in multiple cancer types as well as the subsequent clinical implications of this phenomenon. Thus, the goal of this article collection is to uncover the manifestations of the EMT program with a special emphasis on immunosuppression and regulation of anti-tumor immunity.
We welcome the submission of Original Research articles, Reviews, Methods, Case Reports, and Perspectives including, but not limited to, the following sub-topics:
1. Activation of the EMT program by various innate and adaptive immune cells within the tumor microenvironment
2. Consequences of the EMT program on inducing immune-suppression within the tumor-microenvironment
3. EMT and cancer stem-like cells: regulation of anti-tumor immunity
4. EMT and metastasis: the role of immune cells in regulating the metastatic cascade and influencing the formation of the pre-metastatic niche
5. EMT and dormancy: the role of immune cells in awakening previously dormant cancer cells at distant metastatic sites
6. Regulation of tumor-cell plasticity by immune-suppressive myeloid cells
7. EMT and mechanisms of resistance to immunotherapies
8. Evidence of EMT, immune-evasion, and immune-suppression in clinical settings
The Epithelial-to-Mesenchymal Transition (EMT) is a cell-biological process that operates during embryonic development, wound-healing, and carcinoma progression and facilitates the conversion of epithelial cells to more-mesenchymal derivatives. During this process, cells typically shed the expression of epithelial markers, such as E-Cadherin, and express instead, mesenchymal markers, such as vimentin, fibronectin and certain master EMT-inducing transcription factors (EMT-TFs), notably Zeb1, Twist, Snail and Slug; once expressed, these EMT-TFs regulate the expression of genes associated with the more-mesenchymal state of carcinoma cells. The EMT program is a highly dynamic process that often gives rise to a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal polarization spectrum. Importantly, mesenchymal cells can also lapse back into a more-epithelial state by the reverse process of mesenchymal-to-epithelial transition (MET).
Carcinoma cells that activate the EMT program acquire certain properties such as enhanced invasiveness and motility, enhanced metastatic potential, the gain of tumor-initiating or cancer stem-cell like properties and refractory responses to multiple cytotoxic therapies. Importantly, there is also beginning to emerge a growing appreciation of the ability of mesenchymal carcinoma cells to modulate the tumor microenvironment and drive refractory responses to multiple immunotherapies, including immune checkpoint blockade. In addition to the contextual signals operating within the confines of the primary tumor microenvironment, various immune cells also regulate distinct steps of the metastatic cascade and are functionally important in the formation of the pre-metastatic niche at distant organ sites. The details of the mechanistic maneuvers utilized by carcinoma cells undergoing an EMT to actively evade and suppress anti-tumor immunity opens a new avenue of investigation - one that may likely provide a unique opportunity to sensitize highly refractory mesenchymal cells to immune attack by identifying novel therapeutic targets. An additional unexplored avenue is the generalizability of the EMT program to modulate the immune response in multiple cancer types as well as the subsequent clinical implications of this phenomenon. Thus, the goal of this article collection is to uncover the manifestations of the EMT program with a special emphasis on immunosuppression and regulation of anti-tumor immunity.
We welcome the submission of Original Research articles, Reviews, Methods, Case Reports, and Perspectives including, but not limited to, the following sub-topics:
1. Activation of the EMT program by various innate and adaptive immune cells within the tumor microenvironment
2. Consequences of the EMT program on inducing immune-suppression within the tumor-microenvironment
3. EMT and cancer stem-like cells: regulation of anti-tumor immunity
4. EMT and metastasis: the role of immune cells in regulating the metastatic cascade and influencing the formation of the pre-metastatic niche
5. EMT and dormancy: the role of immune cells in awakening previously dormant cancer cells at distant metastatic sites
6. Regulation of tumor-cell plasticity by immune-suppressive myeloid cells
7. EMT and mechanisms of resistance to immunotherapies
8. Evidence of EMT, immune-evasion, and immune-suppression in clinical settings
