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Transcriptional profiling demonstrates altered characteristics of CD8 + cytotoxic T-cells and regulatory T-cells in TP53-mutated acute myeloid leukemia

Abolhalaj, Milad (författare)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Institutionen för immunteknologi,Institutioner vid LTH,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Sincic, Viktor (författare)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Institutionen för immunteknologi,Institutioner vid LTH,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Lilljebjörn, Henrik (författare)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Translationella genomiska och funktionella studier av leukemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Translational Genomic and Functional Studies of Leukemia,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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Sandén, Carl (författare)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Translationella genomiska och funktionella studier av leukemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Translational Genomic and Functional Studies of Leukemia,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Aab, Alar (författare)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Institutionen för immunteknologi,Institutioner vid LTH,Other operations, LTH,Faculty of Engineering, LTH,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
Hägerbrand, Karin (författare)
Alligator Biosciences AB
Ellmark, Peter (författare)
Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Alligator Biosciences AB
Borrebaeck, Carl (författare)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Institutionen för immunteknologi,Institutioner vid LTH,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Fioretos, Thoas (författare)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Translationella genomiska och funktionella studier av leukemi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Translational Genomic and Functional Studies of Leukemia,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Lundberg, Kristina (författare)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Institutionen för immunteknologi,Institutioner vid LTH,Bioteknik (CI),Utbildningsprogram, LTH,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,Biotechnology (M.Sc.Eng.),Educational programmes, LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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 (creator_code:org_t)
2022-03-16
2022
Svenska.
Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 11:15, s. 3023-3032
Relaterad länk:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: Acute myeloid leukemia (AML) patients have limited effect from T-cell-based therapies, such as PD-1 and CTLA-4 blockade. However, recent data indicate that AML patients with TP53 mutation have higher immune infiltration and other immunomodulatory therapies could thus potentially be effective. Here, we performed the transcriptional analysis of distinct T-cell subpopulations from TP53-mutated AML to identify gene expression signatures suggestive of altered functional properties.Methods: CD8+ cytotoxic T lymphocytes (CTLs), conventional helper T cells (Th), and regulatory T cells (Tregs) were sorted from peripheral blood of AML patients with TP53 mutation (n = 5) and healthy donors (n = 3), using FACS, and the different subpopulations were subsequently subjected to RNA-sequencing. Differentially expressed genes were identified and gene set enrichment analysis (GSEA) was performed to outline altered pathways and exhaustion status. Also, expression levels for a set of genes encoding established and emerging immuno-oncological targets were defined.Results: The results showed altered transcriptional profiles for each of the T-cell subpopulations from TP53-mutated AML as compared to control subjects. IFN-α and IFN-γ signaling were stronger in TP53-mutated AML for both CTLs and Tregs. Furthermore, in TP53-mutated AML as compared to healthy controls, Tregs showed gene expression signatures suggestive of metabolic adaptation to their environment, whereas CTLs exhibited features of exhaustion/dysfunction with a stronger expression of TIM3 as well as enrichment of a gene set related to exhaustion.Conclusions: The results provide insights on mechanisms underlying the inadequate immune response to leukemic cells in TP53-mutated AML and open up for further exploration toward novel treatment regimens for these patients.

Ämnesord

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)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

T-cell
RNA-Sequencing
acute myeloid leukemia (AML)
TP53
Immunotherapy

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art (ämneskategori)
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