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dc.contributor.authorPinzon-Charry, A
dc.contributor.authorMaxwell, T
dc.contributor.authorMcGuckin, MA
dc.contributor.authorSchmidt, C
dc.contributor.authorFurnival, C
dc.contributor.authorLopez, JA
dc.date.accessioned2020-12-18T03:53:38Z
dc.date.available2020-12-18T03:53:38Z
dc.date.issued2006-01-01
dc.identifierpii: bcr1361
dc.identifier.citationPinzon-Charry, A., Maxwell, T., McGuckin, M. A., Schmidt, C., Furnival, C. & Lopez, J. A. (2006). Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. BREAST CANCER RESEARCH, 8 (1), https://doi.org/10.1186/bcr1361.
dc.identifier.issn1465-542X
dc.identifier.urihttp://hdl.handle.net/11343/255965
dc.description.abstractINTRODUCTION: Dendritic cells (DCs) are key antigen-presenting cells that play an essential role in initiating and directing cellular and humoral immunity, including anti-tumor responses. Due to their critical role in cancer, induction of DC apoptosis may be one of the central mechanisms used by tumors to evade immune recognition. METHODS: Spontaneous apoptosis of blood DCs (lineage negative HLA-DR positive cells) was assessed in peripheral blood mononuclear cells (PBMCs) using Annexin-V and TUNEL assays immediately after blood collection. The role of tumor products was assessed by culturing cells with supernatants derived from breast cancer cell lines (TDSN) or PBMCs (PBMC-SN, as a control). The capacity of DC stimulation to prevent apoptosis was assessed by incubating DC with inflammatory cytokines, poly I:C, IL-12 or CD40 ligand (CD40L) prior to culture with TDSN. Apoptosis was determined by flow cytometry and microscopy, and Bcl-2 expression determined by intracellular staining. RESULTS: In this study we document the presence of a significantly higher proportion of apoptotic (Annexin-V+ and TUNEL+) blood DCs in patients with early stage breast cancer (stage I to II; n = 13) compared to healthy volunteers (n = 15). We examined the role of tumor products in this phenomenon and show that supernatants derived from breast cancer lines induce apoptosis of blood DCs in PBMC cultures. Aiming to identify factors that protect blood DC from apoptosis, we compared a range of clinically available maturation stimuli, including inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2 as a cytokine cocktail), synthetic double-stranded RNA (poly I:C) and soluble CD40 ligand. Although inflammatory cytokines and poly I:C induced robust phenotypic maturation, they failed to protect blood DCs from apoptosis. In contrast, CD40 stimulation induced strong antigen uptake, secretion of IL-12 and protected blood DCs from apoptosis through sustained expression of Bcl-2. Exogenous IL-12 provided similar Bcl-2 mediated protection, suggesting that CD40L effect is mediated, at least in part, through IL-12 secretion. CONCLUSION: Cumulatively, our results demonstrate spontaneous apoptosis of blood DCs in patients with breast cancer and confirm that ex vivo conditioning of blood DCs can protect them from tumor-induced apoptosis.
dc.languageEnglish
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.source35th Annual Scientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops
dc.titleSpontaneous apoptosis of blood dendritic cells in patients with breast cancer
dc.typeJournal Article
dc.identifier.doi10.1186/bcr1361
melbourne.affiliation.departmentMedicine Dentistry & Health Sciences
melbourne.source.titleBreast Cancer Research
melbourne.source.volume8
melbourne.source.issue1
melbourne.source.pages513-513
dc.rights.licenseCC BY
melbourne.elementsid1290982
melbourne.contributor.authorMcGuckin, Michael
dc.identifier.eissn1465-5411
melbourne.event.locationMelbourne, AUSTRALIA
melbourne.accessrightsOpen Access


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