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Biological Molecular Imaging Section ... 1 Department of Medical Biology Faculty... 1 Department of Nuclear Medicine La Tim... 1 Laboratory of Molecular Imaging and N... 1 Laboratory of Pathology National Canc... 1 Section on Medical Neuroendocrinology... 1 Section on Medical Neuroendocrinology... 1 Surgical Neurology Branch National In... 1
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Biological Molecular Imaging Section ... 1 Department of Medical Biology Faculty... 1 Department of Nuclear Medicine La Tim... 1 Laboratory of Molecular Imaging and N... 1 Laboratory of Pathology National Canc... 1 Section on Medical Neuroendocrinology... 1 Section on Medical Neuroendocrinology... 1 Surgical Neurology Branch National In... 1
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Caisova, Veronika
Autor Caisova, Veronika Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. veronika.caisova@nih.gov. Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. veronika.caisova@nih.gov
- Li, Liping
- Gupta, Garima
- Jochmanova, Ivana
- Jha, Abhishek
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Uher, Ondrej
Autor Uher, Ondrej Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. ondrej.uher@nih.gov. Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. ondrej.uher@nih.gov
- Huynh, Thanh-Truc
- Miettinen, Markku
- Pang, Ying
- Abunimer, Luma
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PubMed
31083581
DOI
10.3390/cancers11050654
Knihovny.cz E-zdroje
Therapeutic options for metastatic pheochromocytoma/paraganglioma (PHEO/PGL) are limited. Here, we tested an immunotherapeutic approach based on intratumoral injections of mannan-BAM with toll-like receptor ligands into subcutaneous PHEO in a mouse model. This therapy elicited a strong innate immunity-mediated antitumor response and resulted in a significantly lower PHEO volume compared to the phosphate buffered saline (PBS)-treated group and in a significant improvement in mice survival. The cytotoxic effect of neutrophils, as innate immune cells predominantly infiltrating treated tumors, was verified in vitro. Moreover, the combination of mannan-BAM and toll-like receptor ligands with agonistic anti-CD40 was associated with increased mice survival. Subsequent tumor re-challenge also supported adaptive immunity activation, reflected primarily by long-term tumor-specific memory. These results were further verified in metastatic PHEO, where the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 into subcutaneous tumors resulted in significantly less intense bioluminescence signals of liver metastatic lesions induced by tail vein injection compared to the PBS-treated group. Subsequent experiments focusing on the depletion of T cell subpopulations confirmed the crucial role of CD8+ T cells in inhibition of bioluminescence signal intensity of liver metastatic lesions. These data call for a new therapeutic approach in patients with metastatic PHEO/PGL using immunotherapy that initially activates innate immunity followed by an adaptive immune response.
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