Epithelial immune cell-like transition (EIT): A proposed transdifferentiation process underlying immune-suppressive activity of epithelial cancers

The immune system plays a key role in eliminating cancer cells in the body. However, even in fully immune-competent bodies cancers can evade anti-tumor immune action. There is increasing evidence that epithelial cancers can actively suppress anti-tumor immune responses by creating an immune-suppressive micro-environment. It has been reported that epithelial cancers can express immune genes/proteins not normally expressed by their parental tissues, including a variety of cytokines/receptors, immune transcription factors and Ig motifs in cell surface molecules. Recently we observed increased expression of immune genes, including immune-suppressive genes, by prostate epithelial cancers. In view of the above, we propose that immune-suppressive activity of epithelial cancers may stem from their acquisition of immune properties via a transdifferentiation process, we term “Epithelial Immune Cell-like Transition” (EIT), similar to neuroendocrine-like transdifferentiation of prostate adenocarcinoma cells. We propose that the acquired immune properties enable the cancer cells to “communicate” with immune cells, leading to suppression of anti-cancer immune activity in their micro-environment and facilitation of the expansion and malignant progression of the disease. Acquired immune properties of epithelial cancers, which might be quite common, could provide novel targets for reducing cancer-generated immune-suppressive activity and enhancing anti-tumor immune activity. This proposed paradigm shift could lead to novel therapeutic approaches with improved efficacy and broad application.