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  • Hartana, C. A.Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden (author)

Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-08-24
  • WILEY,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-363215
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-363215URI
  • https://doi.org/10.1111/cei.13183DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-151285URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:139213391URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-151934URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Swedish Cancer Society (Cancerfonden); Regional Research Council in Uppsala-Orebro region, Sweden (RFR in Uppsala-Orebro); Swedish Research Council; Cancer Research Foundation in Norrland, Umea, Sweden; Stiftelsen Emil Anderssons fond for medicinsk forskning, Sundsvall, Sweden
  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Bergman, E. AhlenKarolinska Institutet,Karolinska Inst, Sweden (author)
  • Broome, A.Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden (author)
  • Berglund, S.Karolinska Institutet,Karolinska Inst, Sweden (author)
  • Johansson, M.Sundsvall Hosp, Dept Urol, Sundsvall, Sweden,Department of Urology, Sundsvall Hospital, Sundsvall, Sweden (author)
  • Alamdari, F.Vastmanland Hosp, Dept Urol, Vasteras, Sweden (author)
  • Jakubczyk, T.Lanssjukhuset Ryhov, Dept Urol, Jonkoping, Sweden (author)
  • Huge, YlvaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Urologiska kliniken i Östergötland(Swepub:liu)ylvhu61 (author)
  • Aljabery, FirasLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Urologiska kliniken i Östergötland(Swepub:liu)firab05 (author)
  • Palmqvist, K.Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden,Department of Surgery, Östersund County Hospital, Urology section, Östersund, Sweden. (author)
  • Holmström, BennyUppsala universitet,Urologkirurgi,Akad Univ Hosp, Sweden (author)
  • Glise, H.Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden (author)
  • Riklund, KatrineUmeå universitet,Diagnostisk radiologi,Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden(Swepub:umu)kaah0001 (author)
  • Sherif, AmirUmeå universitet,Urologi och andrologi,Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden(Swepub:umu)amsh0008 (author)
  • Winqvist, O.Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden (author)
  • Karolinska InstitutetKarolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden (creator_code:org_t)

Related titles

  • In:Clinical and Experimental Immunology: WILEY194:1, s. 39-530009-91041365-2249

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