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Clinical immunology : the official journal of the Clinical Immunology Society v.183, 2017년, pp.167 - 173   SCI SCIE SCOPUS
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Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade

Grabmeier-Pfistershammer, Katharina (Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria ) ; Stecher, Carmen (Division of Immune Receptors and T cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria ) ; Zettl, Markus (Cancer Immunology and Immune Modulation, Boehringer Ingelheim RCV GmbH & CoKG, Vienna, Austria ) ; Rosskopf, Sandra (Division of Immune Receptors and T cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria ) ; Rieger, Armin (Department of Dermatology, Medical University of Vienna, Vienna, Austria ) ; Zlabinger, Gerhard J. (Division of Clinical and Experimental Immunology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria ) ; Steinberger, Peter (Division of Immune Receptors and T cell Activation, Institute of Immunology, Center for Pathophysiology, ) ;
  • 초록  

    Abstract Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides. Antibodies targeting BTLA and TIM-3 enhanced CD8 T cell proliferation. Moreover, our results indicate that blocking BTLA and TIM-3 in combination with PD-1 might be especially effective in enhancing responses of exhausted human T cells. Highlights PD-1 blockade has a unique potency to enhance T cell response to HIV-1 antigens. BTLA and TIM-3 blockade can augment the PD-1 effect. Combination of immune checkpoint inhibitors could enhance their therapeutic potential. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    PD-1 .   BTLA .   TIM-3 .   CD160 .   LAG-3 .   CTLA-4 .   Immune checkpoints .   Coinhibitory receptors .   T cell exhaustion .   HIV-1.  

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