Plasmacytoid dendritic cells (pDCs) are a unique subset of immune cells originating from the bone marrow, playing a crucial role in the body's innate immune response. They are primarily known for their ability to produce type I interferons (I-IFNs) upon detecting nucleic acids through endosomal Toll-like receptors (TLR) 7 and 9. Recent studies have expanded our understanding of pDCs, revealing their capacity to sense cytosolic DNA via the cGAS-STING pathway, independent of TLR7/9, which also triggers potent I-IFN production. In the context of cancer, pDCs are often found within the tumor microenvironment (TME), where their role remains ambiguous. While they can contribute to cancer immunosurveillance through robust I-IFN responses, their presence in the TME is frequently associated with a tolerogenic phenotype, characterized by low I-IFN production and the promotion of regulatory T cells (Treg). This suggests that the TME may induce a functional state in pDCs that supports tumor progression. Despite these insights, the mechanisms underlying pDC activation and their potential therapeutic reprogramming in cancer remain underexplored, highlighting a significant gap in current research.

This research topic aims to elucidate the complex role of human pDCs in cancer immunity, focusing on their activation, function, and potential therapeutic modulation. Key objectives include defining tumor-associated pDCs (TA-pDCs), understanding the heterogeneity of pDC activation in cancer patients, and identifying immune escape mechanisms induced by the TME. Additionally, the research seeks to explore novel treatment options that can modulate pDC functions to disrupt the immunosuppressive TME and enhance cancer immunosurveillance.

To gather further insights into the multifaceted role of pDCs in cancer, we welcome articles addressing, but not limited to, the following themes:
- Comprehensive characterization of TA-pDCs in various cancer types.
- Analysis of endogenous pDC activation levels and heterogeneity in cancer patients' blood and tissues.
- Investigation of immune escape mechanisms facilitated by the TME in human cancers.
- Evaluation of novel therapeutic strategies targeting pDC functions to enhance anti-tumor immunity.
- Clinical relevance of circulating and tissue pDC enumeration and their interactions during neoadjuvant immunotherapy.
- Integration of single-cell approaches and spatial resolution techniques in cancer tissue analysis.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

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Modulating Plasmacytoid Dendritic Cells: Balancing Cancer Immunity and Tumor Progression