IDENTIFICATION OF ACTIVE COMPONENTS DERIVED FROM NK RESISTANT CELL LINE RESPONSIBLE FOR NK CELL MODULATION

Abstract

1. ABSTRACT There are various mechanism by which, tumors are able to escape from the immune attack of NK cells. The various mechanisms are related to the NK cell adhesion or activation interventions, triggered inhibition and NK cell modulation of effector functions through the interplay of huge pool of receptors on NK cell surface. NK cells are blessed with the innate ability to kill target cell. Thus, they have a major role to defend tumors as well as cells infected by viruses. The sensitivity of infected cell to NK cell lysis may open new prospectives for NK cell-based immunotherapy. Natural Killer cells have been known so far to act against many murine tumors used in experimentation, but in humans their antineoplastic attribute is not agreed upon always. A detailed concept of the mechanisms imposed by the tumor microenvironment in the modulation of cytotoxic immune cells is essential before approving their use in cancer therapies. The multifacet recognition pattern of tumor derived proteins by NK activating receptors and every accessible surface involved in this binding event should be explored. The knowledge of affinity of NK cell receptor with tumor ligands will help in understanding the binding patterns required for the activation of NK cell activity. The interactions between these tumor ligands with their activators are potentially addressable by computational approaches and can further help to develop NK based cancer therapeutic strategies. This thesis aims at investigating new factors released from respective NK sensitive cell line, and to further study the NK cell modulation that results from such factors that can be a potential targets of NK cell based therapy as well as also demonstrated the growth kinetics and growth pattern of the NK sensitive cell line. Various proteins factors were isolated from the supernatants, lysates and whole membrane preparation and separated using SDS-PAGE, which further need to be studied through NK receptor profiling