Role Of Immune Checkpoint Inhibitor TIGIT On NK Cell Activity Against HIV Infection 9227

Abstract Description INTRODUCTION HIV-1 infection enhances the expression of inhibitory molecules on NK cells, leading to impaired NK cell function and immune exhaustion. Our aim is to determine the expression of T cell immunoglobulin and the intracellular tyrosine inhibitory motif domain (TIGIT) in the NK cell response to HIV. Furthermore, we are evaluate whether blocking this inhibitory molecule plays a role in NK cell function to evaluate its potential as a candidate for HIV-1 immunotherapy. MATERIAL&METHODS We evaluated NK cell TIGIT expression in healthy controls and people live with HIV (PLWH) not receiving antiretroviral therapy. NK cell cytotoxic activity and cytokine secretion after TIGIT blockade were analyzed by flow cytometry. RESULT We found that TIGIT was upregulated in ART-naive PLWH NK cells but not in healthy controls NK cells. Another inhibitory receptor, poliovirus receptor-related immunoglobulin domain-containing (PVRIG) expression levels was not showed any significant differences between in healthy controls and PLWH NK cells. IFN γ expression level was found lower in PLWH compared to healthy controls. NK cell activation and degranulation were not increased after TIGIT blockade. CONCLUSION Increased expression levels in ART-naive PLWH compared to healthy controls demonstrate the role of TIGIT in relation to the anti-HIV NK cell response. Clearly, TIGIT blockade was dysfunctional in terms of NK cell cytotoxic activity and cytokine secretion. Funding Sources This project numbered TDK-2023-40139 was supported by Istanbul University Scientific Research Projects Unit. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)