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MALT1 inhibition su...
MALT1 inhibition suppresses antigen-specific T cell responses
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- Kerzeli, Iliana K. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Nasi, Aikaterini (author)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Fletcher, Erika (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Chourlia, Aikaterini (author)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Kallin, Anders (author)
- Medivir AB, Lunastigen 7, S-14144 Huddinge, Sweden.
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- Finnberg, Niklas (author)
- Medivir AB, Lunastigen 7, S-14144 Huddinge, Sweden.
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- Ersmark, Karolina (author)
- Medivir AB, Lunastigen 7, S-14144 Huddinge, Sweden.
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- Lampinen, Maria (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Albertella, Mark (author)
- Medivir AB, Lunastigen 7, S-14144 Huddinge, Sweden.
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- Öberg, Fredrik (author)
- Medivir AB, Lunastigen 7, S-14144 Huddinge, Sweden.
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- Mangsbo, Sara M., 1981- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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(creator_code:org_t)
- Elsevier, 2024
- 2024
- English.
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In: Cellular Immunology. - : Elsevier. - 0008-8749 .- 1090-2163. ; 397
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- The aim of this study was to assess the potential use of a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory T-cells (Tregs). In vitro, MALT1 inhibition suppressed the proteolytic cleavage of the MALT1-substrate HOIL1 and blocked IL-2 secretion in Jurkat cells. It selectively suppressed the proliferation of PBMC-derived Tregs, with no effect on conventional CD4+ T-cells. In vivo, however, no evident anti-tumor effect was achieved by MALT1 inhibition monotherapy or in combination with anti-CTLA4 in the MB49 cancer model. Despite decreased Treg-frequencies in lymph nodes of tumor-bearing animals, intratumoral Treg depletion was not observed. We also showed that MALT1-inhibition caused a reduction of antigen-specific CD8+ T-cells in an adoptive T-cell transfer model. Thus, selective targeting of Tregs would be required to improve the immunotherapeutic effect of MALT1-inhibition. Also, various dosing schedules and combination therapy strategies should be carefully designed and evaluated further.
Subject headings
- 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)
Keyword
- MALT1 inhibition
- T regulatory cells
- T-cell dependent immune surveillance
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kerzeli, Iliana ...
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Nasi, Aikaterini
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Fletcher, Erika
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Chourlia, Aikate ...
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Kallin, Anders
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Finnberg, Niklas
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show more...
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Ersmark, Karolin ...
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Lampinen, Maria
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Albertella, Mark
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Öberg, Fredrik
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Mangsbo, Sara M. ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Cellular Immunol ...
- By the university
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Uppsala University