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- Hu, J., et al.
(författare)
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The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation
- 2013
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 172:3, s. 490-499
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that chemotherapeutic agents may increase the anti-tumoral immune response. Based on the pivotal role of dendritic cells (DCs) in host tumour-specific immune responses, we investigated the effect of commonly used chemotherapeutic drugs dexamethasone, doxorubicin, cisplatin and irinotecan and glucocorticoids on monocyte-derived DCs (moDCs). Dexamethasone displayed the strongest inhibitory effect on DC differentiation. The effect of cisplatin and irinotecan was moderate, while only weak effects were noticed for doxorubicin. Surprisingly, when the functional consequence of chemotherapy-treated CD14+ monocytes and their capacity to activate CD4+ T responders cells were investigated, cisplatin-treated monocytes gave rise to increased T cell proliferation. However, dexamethasone, doxorubicin and irinotecan-pretreated monocytes did not stimulate any increased T cell proliferation. Further investigation of this observation revealed that cisplatin treatment during DC differentiation up-regulated significantly the interferon (IFN)- transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-6 or IFN- transcripts. Blocking IFN- attenuated the cisplatin-enhanced T cell proliferation significantly. In conclusion, cisplatin treatment enhanced the immune stimulatory ability of human monocytes, a mechanism mediated mainly by the increased production of IFN-.
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| 6. |
- Kumar, Archana Vijaya, et al.
(författare)
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HS3ST2 modulates breast cancer cell invasiveness via MAP kinase- and Tcf4 (Tcf7l2)-dependent regulation of protease and cadherin expression
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:11, s. 2579-2592
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2), an enzyme mediating 3-O-sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2-expressing MDA-MB-231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real-time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 -expressing MCF-7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS-dependent basal and FGF2-specific signaling through the constitutively active p44/42 MAPK pathway in MDA-MB-231 cells. Increased MAPK activation was accompanied by upregulation of beta-catenin in MDA-MB-231, and of the transcription factor Tcf4 in both cell lines. Dysregulation of Tcf4-regulated ion transporters and increased cytosolic acidification were observed in HS3ST2-expressing MDA-MB-231 cells, which is a possible underlying cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity.
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| 8. |
- Marits, Per, et al.
(författare)
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The many flavors of tumor-associated B cells
- 2013
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Ingår i: Oncoimmunology. - : Landes Bioscience. - 2162-4011 .- 2162-402X. ; 2:8, s. e25237-
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Tidskriftsartikel (refereegranskat)abstract
- Little is known on the role of distinct B-cell subtypes in human malignancies. We have recently performed a multiplex characterization of B cells in patient-derived tumor-associated tissues, documenting the activation and antigen-driven differentiation of B cells in metastatic lymph nodes and neoplastic lesions. Here we discuss the role of B lymphocytes as antigen-presenting cells and catalysts of T cell-based immunotherapies in view of these findings.
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