Depletion of Plasmacytoid Dendritic Cells Inhibits Tumor Growth and Prevents Bone Metastasis of Breast Cancer Cells

Sawant, Anandi; Hensel, Jonathan A.; Chanda, Diptiman; Harris, Brittney A.; Siegal, Gene P.; Maheshwari, Akhil; Ponnazhagan, Selvarangan

doi:10.4049/jimmunol.1101855

Cited by 165 publications

(126 citation statements)

References 35 publications

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“…It has been confirmed by in vitro co-incubation of tumor cells and macrophages that the substances secreted by macrophages can stimulate the proliferation of tumor cells (11). In vivo tests have shown, through the depletion of macrophages, that TAMs are essential for the growth of different types of tumors (12). GO terms such as 'cell cycle', 'cell proliferation' and 'DNA replication' identified in the present study also support this opinion.…”

Section: Discussionsupporting

confidence: 75%

Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium

Xue

Gao

et al. 2013

Oncology Reports

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Abstract. Many reports have inferred that macrophages can interact with tumor cells in the tumor microenvironment (TME) in a vicious cycle of tumor development; however, the changes in gene expression in tumor cells under the effects of macrophages are still largely unknown. The present study was carried out to illustrate the changes in the gene expression profile in lung cancer cells under the effects of macrophageconditioned medium. Gene expression profile data were derived from the GEO database GSE9315. The GSM234968 sample was derived from a highly invasive human pulmonary adenocarcinoma cell line, CL1-5, and was treated with conditioned medium (supernatant of a culture solution of human monocyte THP-1). The GSM234967 sample that was not treated with the conditioned medium was used as a control. GO and KEGG enrichment analyses were carried out using DAVID software, and visualization networks were constructed using Cytoscape software. The results showed that 40 differentially expressed genes were annotated. Five differentially expressed transcription factors were identified, EIF2B4, EIF2B5, JUNB, GNG11 and HMGB2, which were all related to 'stress' and 'responses'. The gene cluster of JUNB was mainly enriched in cancer-related pathways, 'Wnt signaling pathway' and 'MAPK signaling pathway'. Finally, 10 small molecules, thioridazine, resveratrol, astemizole, ciclopirox, calmidazolium, etoposide, anisomycin, pyrvinium, azacyclonol and terfenadine, which may act on transcription factors, were identified using the CMap database. In conclusion, we identified transcription factors playing key roles in tumor cells under the effects of macrophages in order to provide new clues for blocking this vicious cycle of tumor development.

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Section: Discussionsupporting

confidence: 75%

Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium

Xue

Gao

et al. 2013

Oncology Reports

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“…pDCs have been shown to be accumulated in positive (with metastasis) sentinel lymph nodes in melanoma (18). In mouse models of breast cancer bone metastasis, the depletion of pDCs inhibited tumor growth and prevented metastasis (19). Therefore, the data in the present study provide a rationale for investigating pDCs in the metastasis of gastric cancer.…”

Section: Discussionmentioning

confidence: 80%

Gastric cancer patients have elevated plasmacytoid and CD1c+ dendritic cells in the peripheral blood

Liu

Zhao

et al. 2018

Oncol Lett

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Abstract. Dendritic cells (DCs) are important in tumor immunology. Identifying DC subset markers in the peripheral blood, which are informative for gastric cancer stages, is not only useful for prognosis but may also provide mechanistic insights into processes facilitating therapy. The present study investigated plasmacytoid dendritic cells (pDCs) and myeloid CD1c + dendritic cells (mDC1s) in the peripheral blood of patients with gastric cancer and healthy controls using flow cytometry. Using peripheral DC staining and subset analysis, patients with gastric cancer were identified to have substantially higher numbers of peripheral pDCs and mDC1s. In addition, there was a trend of elevated circulating pDCs with advanced stages and lymph node metastasis in gastric cancer, whereas no differences in circulating mDC1s were observed among the various groups. The results suggested that circulating pDCs are a positive prognostic indicator in patients with gastric cancer of different stages and highlighted the critical role of pDCs immunity in the development of gastric cancer.

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“…To our knowledge this is a unique proof of a direct role of pDC in favoring primary tumor growth in solid tumors. pDC were previously shown to regulate growth of multiple myeloma cells (34) and more recently to favor bone metastasis of breast cancer cells (35).…”

Section: Discussionmentioning

confidence: 99%

Tumor Promotion by Intratumoral Plasmacytoid Dendritic Cells Is Reversed by TLR7 Ligand Treatment

et al. 2013

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Plasmacytoid dendritic cells (pDC) are key regulators of antiviral immunity. In previous studies, we reported that pDC-infiltrating human primary breast tumors represent an independent prognostic factor associated with poor outcome. To understand this negative impact of tumor-associated pDC (TApDC), we developed an orthotopic murine mammary tumor model that closely mimics the human pathology, including pDC and regulatory T cell (Treg) infiltration. We showed that TApDC are mostly immature and maintain their ability to internalize antigens in vivo and to activate CD4 þ T cells. Most importantly, TApDC were specifically altered for cytokine production in response to Toll-like receptor (TLR)-9 ligands in vitro while preserving unaltered response to TLR7 ligands (TLR7L). In vivo pDC depletion delayed tumor growth, showing that TApDC provide an immunesubversive environment, most likely through Treg activation, thus favoring tumor progression. However, in vivo intratumoral administration of TLR7L led to TApDC activation and displayed a potent curative effect. Depletion of pDC and type I IFN neutralization prevented TLR7L antitumoral effect. Our results establish a direct contribution of TApDC to primary breast tumor progression and rationalize the application of TLR7 ligands to restore TApDC activation in breast cancer. Cancer Res; 73(15); 4629-40. Ó2013 AACR.

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Depletion of Plasmacytoid Dendritic Cells Inhibits Tumor Growth and Prevents Bone Metastasis of Breast Cancer Cells

Cited by 165 publications

References 35 publications

Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium

Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium

Gastric cancer patients have elevated plasmacytoid and CD1c+ dendritic cells in the peripheral blood

Tumor Promotion by Intratumoral Plasmacytoid Dendritic Cells Is Reversed by TLR7 Ligand Treatment

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