Table 1.
Epithelial-mesenchymal transition (EMT)-associated changes in the immunological profile of tumor cells.
| Type of Alteration | Consequences | References |
|---|---|---|
| Reduced Expression of Tumor Antigens | ||
| Reduced expression of tumor antigens in melanoma cells | Escape from antigen-specific killing by CTLs | [16] |
| Emergence of antigen-loss variants in EMT tumor cells from neu-transgenic mice | Escape from antigen-specific killing by CTLs | [18] |
| Reduced Expression of Antigen-Presenting Molecules | ||
| Downregulation of HLA class I molecules | Reduced antigen presentation and escape from antigen-specific killing by CTLs. | [20,21] |
| Enhanced Expression of Inhibitory Immune Checkpoint Molecules | ||
| Upregulation of PD-L1, TIM-3, B7-H1, B7-H3, CD47 | Downregulation of antitumor immune responses, resistance to killing by CTLs, amplification of tumor cell EMT | [15,20,22,23,24,25,26,27,28,29,30] |
| Enhanced Resistance of EMT Tumor Cells to Killing by T Cells | ||
| Overexpression of MUC-1 | Reduced susceptibility to killing by TRAIL and CTLs | [31] |
| Expression of the EMT TF brachyury, leading to inefficient apoptosis, with normal levels of HLA class I, antigenic peptides, and components of antigen presentation machinery | Reduced susceptibility to killing by CTLs and NK cells | [32] |
| EMT tumor cells showing defective immune synapse signaling | Resistance to killing by CTLs and NK cells | [33] |
| Upregulation of KLF-4 and downregulation of miR-7 | Reduced susceptibility to killing by CTLs | [34] |
| Expression of hypoxia-inducible miR-210 | Reduced susceptibility to killing by CTLs | [35] |
| Actin cytoskeleton remodeling, autophagy, and attenuation of an immunological synapse | Autophagy-dependent reduced susceptibility to killing by CTLs | [36] |
| Downregulation of HL -I and upregulation of ligands activating NK cells | Reduced recognition by CTLs and enhanced recognition by NK cells | [20,38] |
| Modulation of E-cadherin and CADM1 | Increased susceptibility to killing by NK cells and reduced metastasis formation | [39] |
| EMT-like changes in melanoma cells accompanied by upregulation of HLA class I and downregulation of activating receptors on NK cells | Escape from killing by NK cells | [40] |
Abbreviations: CADM, cell adhesion molecule; CTL, cytotoxic T lymphocyte; EMT, epithelial-mesenchymal transition; HLA, human leukocyte antigen; KLF, Kruppel-like factor; MUC, mucin; NK, natural killer; PD-L, programmed cell death ligand; TF, transcription factor; TIM, T-cell immunoglobulin and mucin domain-containing.