Suppresses metastasis
Metastasis represents the leading cause of cancer-related death mainly owing to the limited efficacy of current anticancer therapies on advanced malignancies. Natural Killer (NK) cells represent an attractive target for cancer immunotherapy owing to their innate capacity to eliminate malignant tumors in a non-Major Histocompatibility Complex (MHC) and non-tumor antigen-restricted manner. Significant experimental evidence exists in support of a role for NK cells in suppression of metastasis formation.
Fundamental Role For NK cells In Prevention Of Metastasis
In a landmark paper, Kim et al. evaluated the contribution of NK cells to in vivo tumor formation in transgenic mice which could be selectively depleted of NK cells but develop functionally normal B, T, and NK/T Cells. The authors observed significantly greater liver and lung metastases in animals lacking NK cells, and this effect was only partially rescued by NK/T and T cells, suggesting a fundamental role for NK cells in prevention of metastasis.
NK Mediated Immune Surveillance Of Pre-Metastasis Tumors
Lopez-Soto et al demonstrated a provocative link between the acquisition of epithelial-mesenchymal transition (EMT)* characteristics in human colon cancer cell lines and archived human colon cancer samples in the upregulation of activating NK ligands, including MHC class I chain-related molecules A and B, providing further evidence in support of NK mediated immune surveillance of pre-metastasis tumors with possible preferential targeting of cancer stem cells.
*Note: the epithelial-mesenchymal transition is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these cells can differentiate into a variety of cell types. EMT is essential to numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.
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