Role of the ITAM-Bearing Receptors Expressed by Natural Killer Cells in Cancer

Abstract

Natural Killer (NK) cells are innate lymphoid cells (ILCs) capable of recognizing and directly killing tumor cells. They also secrete cytokines and chemokines, which participate in the shaping of the adaptive response. NK cells identify tumor cells and are activated through a net positive signal from inhibitory and activating receptors. Several activating NK cell receptors are coupled to adaptor molecules containing an immunoreceptor tyrosine-based activation motif (ITAM). These receptors include CD16 and the natural cytotoxic receptors NKp46, NKp44, NKp30 in humans. The powerful antitumor NK cell response triggered by these activating receptors has made them attractive targets for exploitation in immunotherapy. In this review, we will discuss the different activating receptors associated with ITAM-bearing cell surface receptors expressed on NK cells, their modulations in the tumor context and the various therapeutic tools developed to boost NK cell responses in cancer patients.

Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer

“…Human NK cells comprise two main subsets, the cytotoxic CD16 + CD56 dim (CD16 + ) cells and the cytokine-producing CD56 bright cells ( 31, 32 ). Surgery-induced accumulation of M-MDSC coincided with reduced counts and frequencies of CD16 + NK cells and CD56 bright NK cells ( Fig.…”

Advances in research on immune escape mechanism of glioma

“…Under physiological conditions, the normal function of NK cells is regulated and conditioned by both activating and inhibiting signals 73 . However, some tumor cells can cause changes in NK cell function through different regulatory mechanisms that prevent them from performing their normal immunosurveillance function, resulting in tumor cells evading immunosurveillance 74 . The approaches for NK Cell Immunotherapy were displayed in Figure 5.…”

Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer

“…NK cells are controlled by an array of activating and inhibitory receptors and their activation is dependent on a delicate balance between these signals. Activating receptors include NKp46, NKG2D, NKp44, NKp30, NKG2C and activating killer cell immunoglobulin-like receptors (KIR) (reviewed in [7][8][9]). The main inhibitory receptors expressed by NK cells are NKG2A and the inhibitory KIR [9].…”