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Tissue-resident mem...
Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer
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- Hartana, C. A. (author)
- Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden
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- Bergman, E. Ahlen (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Broome, A. (author)
- Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden
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- Berglund, S. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Johansson, M. (author)
- Sundsvall Hosp, Dept Urol, Sundsvall, Sweden,Department of Urology, Sundsvall Hospital, Sundsvall, Sweden
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- Alamdari, F. (author)
- Vastmanland Hosp, Dept Urol, Vasteras, Sweden
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- Jakubczyk, T. (author)
- Lanssjukhuset Ryhov, Dept Urol, Jonkoping, Sweden
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- Huge, Ylva (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Urologiska kliniken i Östergötland
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- Aljabery, Firas (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Urologiska kliniken i Östergötland
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- Palmqvist, K. (author)
- Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden,Department of Surgery, Östersund County Hospital, Urology section, Östersund, Sweden.
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- Holmström, Benny (author)
- Uppsala universitet,Urologkirurgi,Akad Univ Hosp, Sweden
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- Glise, H. (author)
- Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden
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- Riklund, Katrine (author)
- Umeå universitet,Diagnostisk radiologi,Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden
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- Sherif, Amir (author)
- Umeå universitet,Urologi och andrologi,Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden
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- Winqvist, O. (author)
- Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden
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(creator_code:org_t)
- 2018-08-24
- 2018
- English.
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In: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 194:1, s. 39-53
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Abstract
Subject headings
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- Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (329% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.
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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- CD8-positive T lymphocytes
- cell exhaustion
- DNA methylation
- perforin
- tissue-resident memory T cells
- urinary bladder neoplasms
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hartana, C. A.
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Bergman, E. Ahle ...
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Broome, A.
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Berglund, S.
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Johansson, M.
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Alamdari, F.
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show more...
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Jakubczyk, T.
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Huge, Ylva
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Aljabery, Firas
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Palmqvist, K.
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Holmström, Benny
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Glise, H.
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Riklund, Katrine
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Sherif, Amir
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Winqvist, O.
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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 ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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Clinical and Exp ...
- By the university
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Uppsala University
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Umeå University
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Karolinska Institutet
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Linköping University