Scholarlink

<p>Natural Killer (NK) cells are promising candidates for targeting persistently infected CD4 + T cells in people with HIV-1 (PWH). However, chronicity of HIV-1 infection impairs NK cell functionality, requiring additional strategies to potentiate their cytotoxic activity. This study demonstrates that dendritic cells primed with nanoparticles containing Poly I:C (Nano-PIC-MDDC) enhance the natural cytotoxic function of NK cells from effective responder PWH. These NK cells exhibit increased proportions of NKG2C+ cell subsets capable of eliminating HIV-1 infected CD4 + T cells through the TRAIL receptor. In contrast, in non-responder PWH, elevated expression of the inhibitory receptor TIGIT is associated with reduced frequencies of NKG2C + NK cells and diminished TRAIL expression. TIGIT blockade restores cytotoxicity of NK cells from non-responder PWH against HIV-1-infected cells by upregulating TRAIL. Furthermore, combining Nano-PIC-MDDC-primed NK cells with anti-TIGIT immunotherapy in humanized NSG mice reduces the expansion of HIV-1 infected cells, preserves NKG2C + NK cell precursors and increases TRAIL expression in tissue. Collectively, these findings support the combined use of Nano-PIC-MDDC and TIGIT blockade as a promising immunotherapeutic strategy toward an HIV-1 cure.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Combined dendritic cell and anti-TIGIT immunotherapy potentiates adaptive NK cells against HIV-1

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月5日

查看全文
  • Ildefonso Sánchez-Cerrillo,
  • María Agudo-Lera,
  • Olga Popova,
  • Ilya Tsukalov,
  • Marta Calvet-Mirabent,
  • Ignacio de los Santos,
  • Lucio García-Fraile,
  • Patricia Fuentes,
  • Cristina Delgado-Arévalo,
  • Juan Alcain,
  • Nerea Sánchez-Gaona,
  • Judith Grau-Expósito,
  • María Lázaro-Díez,
  • Cecilia Muñoz-Calleja,
  • Arantzazu Alfranca,
  • Meritxell Genescà,
  • Julia G Prado,
  • Vladimir Vrbanac,
  • Alejandro Balazs,
  • María José Buzón,
  • María L Toribio,
  • María A Muñoz-Fernández,
  • Francisco Sánchez-Madrid,
  • Enrique Martín-Gayo

摘要

Natural Killer (NK) cells are promising candidates for targeting persistently infected CD4 + T cells in people with HIV-1 (PWH). However, chronicity of HIV-1 infection impairs NK cell functionality, requiring additional strategies to potentiate their cytotoxic activity. This study demonstrates that dendritic cells primed with nanoparticles containing Poly I:C (Nano-PIC-MDDC) enhance the natural cytotoxic function of NK cells from effective responder PWH. These NK cells exhibit increased proportions of NKG2C+ cell subsets capable of eliminating HIV-1 infected CD4 + T cells through the TRAIL receptor. In contrast, in non-responder PWH, elevated expression of the inhibitory receptor TIGIT is associated with reduced frequencies of NKG2C + NK cells and diminished TRAIL expression. TIGIT blockade restores cytotoxicity of NK cells from non-responder PWH against HIV-1-infected cells by upregulating TRAIL. Furthermore, combining Nano-PIC-MDDC-primed NK cells with anti-TIGIT immunotherapy in humanized NSG mice reduces the expansion of HIV-1 infected cells, preserves NKG2C + NK cell precursors and increases TRAIL expression in tissue. Collectively, these findings support the combined use of Nano-PIC-MDDC and TIGIT blockade as a promising immunotherapeutic strategy toward an HIV-1 cure.