• Je něco špatně v tomto záznamu ?

The Significant Reduction or Complete Eradication of Subcutaneous and Metastatic Lesions in a Pheochromocytoma Mouse Model after Immunotherapy Using Mannan-BAM, TLR Ligands, and Anti-CD40

V. Caisova, L. Li, G. Gupta, I. Jochmanova, A. Jha, O. Uher, TT. Huynh, M. Miettinen, Y. Pang, L. Abunimer, G. Niu, X. Chen, HK. Ghayee, D. Taïeb, Z. Zhuang, J. Zenka, K. Pacak,

. 2019 ; 11 (5) : . [pub] 20190511

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19029023

Grantová podpora
ZIAHD008735 Foundation for the National Institutes of Health

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19029023
003      
CZ-PrNML
005      
20190815114704.0
007      
ta
008      
190813s2019 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/cancers11050654 $2 doi
035    __
$a (PubMed)31083581
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Caisova, Veronika $u 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.
245    14
$a The Significant Reduction or Complete Eradication of Subcutaneous and Metastatic Lesions in a Pheochromocytoma Mouse Model after Immunotherapy Using Mannan-BAM, TLR Ligands, and Anti-CD40 / $c V. Caisova, L. Li, G. Gupta, I. Jochmanova, A. Jha, O. Uher, TT. Huynh, M. Miettinen, Y. Pang, L. Abunimer, G. Niu, X. Chen, HK. Ghayee, D. Taïeb, Z. Zhuang, J. Zenka, K. Pacak,
520    9_
$a 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.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Li, Liping $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. bat.150@hotmail.com.
700    1_
$a Gupta, Garima $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. garima.gupta83@gmail.com.
700    1_
$a Jochmanova, Ivana $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. ivana.jochmanova@gmail.com.
700    1_
$a Jha, Abhishek $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. abhishek.jha@nih.gov.
700    1_
$a Uher, Ondrej $u 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.
700    1_
$a Huynh, Thanh-Truc $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. huynht@mail.nih.gov.
700    1_
$a Miettinen, Markku $u Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. markku.miettinen@nih.gov.
700    1_
$a Pang, Ying $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. ying.pang@nih.gov.
700    1_
$a Abunimer, Luma $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. luma.abunimer@nih.gov.
700    1_
$a Niu, Gang $u Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20814, USA. gang.niu@nih.gov.
700    1_
$a Chen, Xiaoyuan $u Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20814, USA. shawn.chen@nih.gov.
700    1_
$a Ghayee, Hans Kumar $u Biological Molecular Imaging Section, University of Florida College of Medicine, Gainesville, FL 32603, USA. Hans.Ghayee@medicine.ufl.edu.
700    1_
$a Taïeb, David $u Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, 13385 Marseille, France. David.TAIEB@ap-hm.fr.
700    1_
$a Zhuang, Zhengping $u Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA. zhengping.zhuang@nih.gov.
700    1_
$a Zenka, Jan $u Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. jzenka@gmail.com.
700    1_
$a Pacak, Karel $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814, USA. karel@mail.nih.gov.
773    0_
$w MED00173178 $t Cancers $x 2072-6694 $g Roč. 11, č. 5 (2019)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31083581 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190813 $b ABA008
991    __
$a 20190815114932 $b ABA008
999    __
$a ind $b bmc $g 1434172 $s 1067483
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 11 $c 5 $e 20190511 $i 2072-6694 $m Cancers $n Cancers $x MED00173178
GRA    __
$a ZIAHD008735 $p Foundation for the National Institutes of Health
LZP    __
$a Pubmed-20190813

Najít záznam

Citační ukazatele

Možnosti archivace