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IL-15 activates mTO...
IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells
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- Mao, Yumeng (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;
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- van Hoef, Vincent (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden;
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- Zhang, Xiaonan (författare)
- Karolinska Institutet,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;;Department of Medical and Health Sciences, Linköping University, Linköping, Sweden;
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- Wennerberg, Erik (författare)
- Karolinska Institute, Sweden; Weill Cornell Med, NY USA,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;;Department of Radiation Oncology, Weill Cornell Medicine, New York, NY; and
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- Lorent, Julie (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden;
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- Witt, Kristina (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;
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- Masvidal, Laia (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden;
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- Liang, Shuo (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden;
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- Murray, Shannon (författare)
- Nova Southeastern University, FL USA,Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL
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- Larsson, Ola (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Karolinska Institutet, SciLifeLab, Solna, Sweden;
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- Kiessling, Rolf (författare)
- Karolinska Institutet,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;
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- Lundqvist, Andreas (författare)
- Karolinska Institutet,Karolinska Institute, Sweden; Nova Southeastern University, FL USA,Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden;;Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL
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(creator_code:org_t)
- AMER SOC HEMATOLOGY, 2016
- 2016
- Engelska.
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 128:11, s. 1475-1489
- Relaterad länk:
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https://ashpublicati...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Treatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor postinfusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK-cell functions following cytokine withdrawal to model postinfusion performance. In contrast to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided cell function advantages. Genome-wide analysis of cytosolic and polysome-associated messenger RNA (mRNA) revealed not only cytokine-dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mammalian target of rapamycin (mTOR) signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced cell function advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK-cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15-stimulated NK cells was also observed using a clinically applicable protocol for NK-cell expansion in vitro and in vivo. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B-cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR-regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Blood
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- Av författaren/redakt...
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Mao, Yumeng
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van Hoef, Vincen ...
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Zhang, Xiaonan
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Wennerberg, Erik
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Lorent, Julie
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Witt, Kristina
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visa fler...
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Masvidal, Laia
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Liang, Shuo
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Murray, Shannon
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Larsson, Ola
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Kiessling, Rolf
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Lundqvist, Andre ...
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- MEDICIN OCH HÄLSOVETENSKAP
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Blood
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Linköpings universitet
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Karolinska Institutet
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