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- Wennerberg, Erik, et al.
(författare)
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Doxorubicin sensitizes human tumor cells to NK and T cell-mediated killing by augmented TRAIL-receptor signaling
- 2013
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1097-0215 .- 0020-7136.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Doxorubicin (DOX) is an anthracycline antibiotic that is widely used to treat different types of malignancy. In this study, it was studied whether DOX could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with subapoptotic doses of DOX sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7% increase in lysis (2.5 mean fold increase, p < 0.0001) and a 2.9 to 14.2% increase in lysis (3.0 mean-fold increase, p < 0.05), respectively. The sensitizing effect of the drug was primarily dependent on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL-receptor signaling, but not on Fas-ligand, perforin, NKG2D or DNAM-1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL-R2 on DOX-treated tumor cells and by downregulation of cellular FLICE inhibitory protein, the inhibitors of death receptor-mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with DOX showed increased processing and activation of caspase-8 on coculture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor-bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p < 0.05) or T cells (p < 0.0001) following DOX treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following DOX treatment not only delayed tumor progression but also significantly improved the long-term survival (p < 0.01). Based on these findings, it was proposed that DOX can be used to improve the efficacy of adoptive cell therapy in patients with cancer.
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| 2. |
- Akre, O, et al.
(författare)
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Similar at a glance, but not the same
- 2008
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 123:6, s. 1480-1480
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Beskow, Anna H., et al.
(författare)
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Interaction of host and viral risk factors for development of cervical carcinoma in situ
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 117:4, s. 690-692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Infection by oncogenic human papillomavirus (HPV) is a necessary but not sufficient cause of cervical carcinoma. Several host genetic and viral factors have been reported to increase the risk of carcinoma development given an HPV infection. In our study, we have analysed the contribution of HPV 16 E6 sequence subtype and allelic variation at human leukocyte antigen (HLA) class II loci to the risk of developing cervical carcinoma in situ. Non-European-like HPV 16 E6 sequence subtypes were not found to be associated with an increased risk of cervical carcinoma, as compared to European-like variants. However, an association was found between the HPV 16 E6 L83V variant and the DR*04-DQ*03 haplotype. This association has been observed in several independent studies and shows that both the host HLA class II genotype and viral subtype will affect the risk of an infection progressing into cervical carcinoma.
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