EMT in immuno-resistance.

Although the advent of new immunotherapy approaches has improved survival for many patients with advanced malignancies, the high degree of nonresponders, especially in highly prevalent malignancies including breast, colon and prostate cancers was also a strong reminder that we possess only partial understanding of the events underlying the immune resistance of tumors. Considerable evidence indicates that the innate and adaptive immune systems participate in the recognition and destruction of cancer cells by a process known as cancer immunosurveillance. Tumor antigen-specific cytotoxic T-lymphocytes (CTL) are the major effectors in the immune response against tumor cells, and current approaches are essentially designed with the ultimate goal of inducing a strong CTL response. It is now obvious that some tumor cells can escape immunosurveillance, and accumulating evidence suggests such escape is tightly controlled by the tumor microenvironment, metabolic remodeling/hypoxia, cellular complexity and plasticity. As we develop a more complete view on the multifaceted role of tumor microenvironment in tumor development, progression, and in shaping tumor stroma, emerging observations now provide support for an essential role of tumor plasticity in resistance to CTL attacks. Along this line, epithelial mesenchymal transition (EMT) is an effective strategy by which cancer cells could gain plasticity. EMT is a transdifferentiation process whereby epithelial cells lose their epithelial properties while gaining mesenchymal properties [1]. At least a fraction of cancer cells can activate this process in response to various stimuli while they may acquire in addition a drug resistant phenotype and an increased ability to invade which is a prerequisite for entry into the circulation (as Circulating Tumor Cells) and metastatic dissemination [1]. EMT can be partial or reversible (Figure 1). This implies the existence of distinct and potentially variable Editorial