Microenvironment and Immunology Quantitative and Functional Alterations of Plasmacytoid Dendritic Cells Contribute to Immune Tolerance in Ovarian Cancer
نویسندگان
چکیده
In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4þCD123þBDCA2þ pDC were the most abundant dendritic cell subset; however, they were profoundly depleted in peripheral blood. The presence of pDC in primary ovarian cancer, but not ascites, was an independent prognostic factor associated with early relapse. Following chemotherapy, we observed a partial restoration of blood pDC levels in patients in complete remission. These findings show preferential recruitment of pDC into tumors where they express a partially mature phenotype that may reflect an in situ activation. Importantly, compared with pDC found in ascites or blood, tumor-associated pDC (TApDC) produced less IFN-a, TNF-a, IL-6, macrophage inflammatory protein-1b, and RANTES in response to toll-like receptor stimulation, and alterations in pDC functions were mainly mediated through tumor-derived TNF-a and TGF-b. Unlike ascites-derived pDC, TApDC induced IL-10 production from allogeneic naive CD4þ T lymphocytes, suggesting the existence of a paracrine immunosuppressive loop. Taken together, our findings indicate that both local and systemic dysfunction of pDC play a critical role in the progression of ovarian cancer via induction of immune tolerance. Cancer Res; 71(16); 5423–34. 2011 AACR.
منابع مشابه
Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer.
In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4(+)CD123(+)BDCA2(+) pDC were the m...
متن کاملDendritic Cells in Transplant Tolerance
Dendritic cells (DCs) are a heterogeneous family of professional APCs involved in priming adaptive immune responses. Donor DCs (direct pathway of allorecognition) and recipient DCs presenting processed donor major histocompatibility complex (MHC) as peptides (indirect pathway of allorecognition) participate actively in graft rejection by stimulating recipient T cell responses following organ tr...
متن کاملPlasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma.
To directly dissect the role of each immune component in human tumor immunopathogenesis, we have studied the interaction between dendritic cells and T cells in the tumor environment of patients with ovarian carcinoma. We previously reported that functional plasmacytoid dendritic cells, but not functionally mature myeloid dendritic cells, accumulated in tumor microenvironments. We now show that ...
متن کاملPlasmacytoid dendritic cells in angiolymphoid hyperplasia with eosinophilia
Background: Angiolymphoid hyperplasia with eosinophilia (ALHE) is characterized by irregularly-shaped blood vessels with an inflammatory infiltrate. While absent from normal skin, plasmacytoid dendritic cells (pDCs) infiltrate the skin upon injury and during several infectious, inflammatory, and neoplastic entities. In addition to providing anti-viral resistance, pDCs link the innate and adapti...
متن کاملDendritic Cells and Their Role in Cancer Immunotherapy
Dendritic cells (DCs) are antigen presenting cells with unique capability to take up and process antigens in the peripheral blood and tissues. They subsequently migrate to draining lymph nodes where they present these antigens and stimulate naive T lympho-cytes. During their life cycle, DCs go through two maturation stages and are referred to as immature and mature cells, respectively. While im...
متن کامل