REGULATION OF EXPRESSION OF NK CELL RECEPTOR BY TUMOUR DERIVED TRANSCRIPTION FACTOR

Abstract

Natural killer (NK) cells were identified 30 years ago based on their ability to "spontaneously" kill tumour cells. The NK cell recognition and activation is due to presence of receptors that binds to specific ligands on tumour cells and normal cells. These receptors have the ability to modulate and activate NK cell function. NK cell response is regulated by the balance between the signals by activating and inhibitory receptors. The outcome of immune response is determined by the extent of strength of activating and inhibitory signals. The expressions of inhibitory receptor were found to be up regulating and activating receptor is down regulating against tumour cell. Tumour cell had reported in escape NK mediated recognition by down regulating the expression of ligands for activating receptors and over expressing the ligand for inhibitory receptors. NK cell inhibitory function can be a means for promotion and regression of tumour and exploring means of blockade of NK cell inhibitory receptors is a way to promote immune response against tumour. Cancer therapies are being developed based on preventing NK cell inhibition or activation of NK cell receptors and modulation of T cell function. Transcription factors (TFs) are key molecules in the regulation of gene transcription and have a significant influence on immune cells growth and development. Many primary and modified genes leading to cancer, participate in many pathways of NK cell development and maturation. Tumours are essentially tissues that have overcome normal regulation mechanisms, and therefore the ability to distinguish normal cells from abnormal cells is a key part of selectively attacking tumour cells. TF derived from tumour cells like GATA -3, ER β, Helios A, bind on the 5’UTR region of NK cell inhibitory receptor genes and modulate their normal regulation by affecting their signaling pathways. These tumour derived TF up regulate and down regulate the signaling of NK cell and abnormalities in signaling pathway leads to progression of tumour cells. Understanding the NK cell receptors and their recognition mechanisms provides new ways for the development of immunotherapies against cancer.