Distinct roles of PGE2 signaling via EP2 and EP4 in circulating pDCs: Implications for immune modulation in the tumor microenvironment

• DOI: 10.1093/jleuko/qiaf034
• Publication Date: 2025-03-23T04:49:58Z
• Authors: Jorge Cuenca-Esca...; Mark W D Sweep; Mark A J Gorris; Tjitske Duiveman-...; Alessandra Cambi; Georgina Flórez-Grau; Jolanda M de Vries
• Keywords: Prostaglandin E2 receptor

Dendritic cells (DCs) play a pivotal role in orchestrating adaptive immunity response to environmental cues such as prostaglandin E2 (PGE2). Tumors are known establish microenvironment rich PGE2. Tumor-derived PGE2 is regarded mediator of regulatory features DCs, facilitating immune evasion and tumor progression. In the effects mediated through E-prostanoid receptor type 2 (EP2) EP4. While immunomodulatory signaling via EP2/4 monocyte-derived DCs (moDCs) well-established, its human blood plasmacytoid (pDCs) poorly characterized. Therefore, this study we investigated effect EP2 EP4 on pDC function, well relevance modulating these receptors pDCs exposed tumor-derived Our findings reveal that exhibit distinct functions pDCs. PGE2-EP4 mediates upregulation maturation markers (e.g., CD83 HLA-DR), enhances CCR7-based migratory impairs production pro-inflammatory mediators IFNα CXCL9) stimulates expansion CD8 T with marked suppressive phenotype. contrast, PGE2-EP2 hinders induces character. Additionally, using different vitro models, show blockade modulates phenotype Together, results identify distinctive illustrate potential therapeutic benefit targeting axis mitigate tumor-induced dysfunction.