Tumor microenvironment converts plasmacytoid dendritic cells into immunosuppressive/tolerogenic cells: insight into the molecular mechanisms

• Published in: Journal of leukocyte biology Vol. 93; no. 3; pp. 343 - 352
• Main Authors: Demoulin, Stéphanie, Herfs, Michael, Delvenne, Philippe, Hubert, Pascale
• Format: Journal Article Web Resource
• Language: English
• Published: United States Society for Leukocyte Biology 01.03.2013; Wiley Liss, Inc
• Subjects: Animals; antitumor immunity; cancer; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Dendritic Cells - immunology; Dendritic Cells - pathology; Human health sciences; Humans; Immune Tolerance; immunosuppression; Interferon Type I - immunology; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Oncologie; Oncology; Plasma Cells - immunology; Plasma Cells - pathology; Sciences de la santé humaine; Tumor Escape; Tumor Microenvironment - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0812397

Review of neoplastic lesions associated with infiltration of immunosuppressive pDC and the molecular pathways developed by tumors, to prevent antitumoral pDC responses. Human pDCs represent a rare population of circulating cells characterized by a rapid and massive TLR‐dependent secretion of type I IFN in response to pathogenic agents or danger signals. Through their capacity to bring together innate and adaptive immunity and to secrete soluble factors controlling cancer development, these cells could represent important actors in antitumor immunity. However, accumulating evidence suggests that pDCs recruited to the tumor microenvironment often display a nonactivated state and are associated with the development and maintenance of immunosuppression. Here, we present an overview of neoplastic lesions associated with an infiltration of immunosuppressive/tolerogenic pDC. Moreover, as the proper response of pDC against cancer depends on a critical balance between immune‐activating and immune‐suppressing mechanisms, we summarize current knowledge about the molecular pathways developed by tumors to prevent antitumoral pDC immune responses. A better understanding of the mechanisms regulating pDC function in tumors could aid in the development of new therapies. Indeed, effective cancer vaccines or therapies could combine immunoactivating strategies (i.e., TLR agonists) with elimination of immune‐suppressing mechanisms, leading to pDC reprogramming and thus, allowing tumor rejection in a clinical setting.