Combined dendritic cell and anti-TIGIT immunotherapy potentiates adaptive NK cells against HIV-1
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44321_2025_Article_255.pdf
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Author(s)
Sánchez-Cerrillo, Ildefonso
Agudo-Lera, María
Popova, Olga
Tsukalov, Ilya
Calvet-Mirabent, Marta
de los Santos, Ignacio
García-Fraile, Lucio
Fuentes, Patricia
Delgado-Arévalo, Cristina
Alcain, Juan
Date Issued
July 2025
Journal
EMBO Molecular Medicine
Publisher
Nature Publishing Group UK
Citation
Sánchez-Cerrillo, Ildefonso, Agudo-Lera, María, Popova, Olga, Tsukalov, Ilya, Calvet-Mirabent, Marta et al. 2025. "Combined dendritic cell and anti-TIGIT immunotherapy potentiates adaptive NK cells against HIV-1." EMBO Molecular Medicine, 17 (7).
Version
Final published version
Abstract
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.
MIT Department
Ragon Institute of MGH, MIT and Harvard
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DOI of Published Version
https://doi.org/10.1038/s44321-025-00255-x
