Mechanisms of Tumor and Viral Immune Escape from Natural Killer Cell-Mediated Surveillance

Abstract

Human natural killer (NK) cells recognize and efficiently eliminate MHC class I low or negative malignant targets and virally infected host cells, without requirement for prior sensitization. However, viruses and various tumor cells display elaborate adaptations to evade and overcome immunosurveillance. The current review focuses on escape mechanisms of viruses and malignantly transformed ‘stressed’ cells to evade from NK cell cytotoxicity. A general overview of recent clinical studies using allogeneic donor NK cells is given, summarizing first data about a possible benefit for patients suffering from high-risk leukemia and solid tumors. Finally, the review discusses the future perspectives and hypotheses aiming to improve therapeutic NK cell strategies against tumor immune escape mechanisms.

NK Cells in Central Nervous System Disorders

“…Thus, decreased expression of NKG2D was shown on NK cells that were isolated from GBM patients (24). This downmodulation of NK cell functions in brain tumors reflects a common mechanism of immune escape found in other solid tumors (25). Infections of the CNS.…”

Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells

“…Other substances that target the shedding of NKG2DL are also being explored to enhance CD8 C T cell cytotoxic killing of cancer cells. 39 Influencing T-cell trafficking Although cytotoxic T cells are likely to play a role in eliminating tumors, failure to access the target tumor tissue presents a critical obstacle. Tumors may influence T-cell trafficking by downregulating adhesion molecules such as ICAM-1/2, VCAM-1, and CD34 in their vessel component to prevent T cells from infiltrating the tumor.…”

The Stalk Domain and the Glycosylation Status of the Activating Natural Killer Cell Receptor NKp30 Are Important for Ligand Binding

“…2 cells are large granular lymphocytes of the innate immune system that spontaneously kill foreign, tumor, and virus-infected cells (1)(2)(3). Additionally, NK cells act as immune regulators by secretion of chemokines and cytokines and/or by direct interaction with other immune cells such as dendritic cells (DCs) (4,5).…”