The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid–rich tumor microenvironment
Abstract
Plasmacytoid dendritic cells (pDCs) are specialized immune cells best known for their ability to produce large amounts of type I interferons (IFN-I) upon nucleic acid sensing through endosomal Toll-like receptors (TLR)-7/8 and 9. In tumors, the accumulation of nucleic acids (NAs) deriving from extensive cancer cell death would be expected to activate pDCs and induce IFN-I–mediated anti-tumor responses. However, tumor-infiltrating pDCs typically exhibit impaired IFN-I production and instead acquire immunosuppressive properties, revealing a paradox between NAs availability and pDC function within the tumor microenvironment (TME). In this review, we examine current knowledge and explore the mechanisms that may constrain IFN-I responses by pDCs, including chronic stimulation, alterations in TLR signaling and limited accessibility of tumor-derived NAs. We discuss key open questions regarding how tumor-associated signals may impair pDC responsiveness and contribute to their dysfunction, the nature and immunostimulatory potential of tumor-derived NAs, and their intracellular delivery. By highlighting these unresolved questions, we propose conceptual frameworks to better understand pDC biology in cancer and identify strategies to restore their IFN-I–mediated antitumor functions.
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BibTeX
@article{vasilakou2026plasmacytoid,
title = {{The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid–rich tumor microenvironment}},
author = {Aliki Vasilakou and Séverine Loizon and Maxime Dubois and Paôline Laurent and Vanja Sisirak and Dorothée Duluc},
journal = {Frontiers in Immunology},
year = {2026},
month = jul,
doi = {10.3389/fimmu.2026.1847012},
url = {https://u-bordeaux.hal.science/hal-05737698v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid–rich tumor microenvironment
AU - Aliki Vasilakou
AU - Séverine Loizon
AU - Maxime Dubois
AU - Paôline Laurent
AU - Vanja Sisirak
AU - Dorothée Duluc
PY - 2026
DA - 2026/07/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1847012
UR - https://u-bordeaux.hal.science/hal-05737698v1
AB - Plasmacytoid dendritic cells (pDCs) are specialized immune cells best known for their ability to produce large amounts of type I interferons (IFN-I) upon nucleic acid sensing through endosomal Toll-like receptors (TLR)-7/8 and 9. In tumors, the accumulation of nucleic acids (NAs) deriving from extensive cancer cell death would be expected to activate pDCs and induce IFN-I–mediated anti-tumor responses. However, tumor-infiltrating pDCs typically exhibit impaired IFN-I production and instead acquire immunosuppressive properties, revealing a paradox between NAs availability and pDC function within the tumor microenvironment (TME). In this review, we examine current knowledge and explore the mechanisms that may constrain IFN-I responses by pDCs, including chronic stimulation, alterations in TLR signaling and limited accessibility of tumor-derived NAs. We discuss key open questions regarding how tumor-associated signals may impair pDC responsiveness and contribute to their dysfunction, the nature and immunostimulatory potential of tumor-derived NAs, and their intracellular delivery. By highlighting these unresolved questions, we propose conceptual frameworks to better understand pDC biology in cancer and identify strategies to restore their IFN-I–mediated antitumor functions.
SN - 1664-3224
SN - 1664-3224
ER -