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Sökning: id:"swepub:oai:DiVA.org:kth-269481" > Boosting Natural Ki...

  • Sayitoglu, Ece CananNova Southeastern Univ, Dr Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA. (författare)

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • 2020-01-28
  • FRONTIERS MEDIA SA,2020
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-269481
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-269481URI
  • https://doi.org/10.3389/fimmu.2020.00040DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:143000226URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20200309
  • Sarcomas are malignancies of mesenchymal origin that occur in bone and soft tissues. Many are chemo- and radiotherapy resistant, thus conventional treatments fail to increase overall survival. Natural Killer (NK) cells exert anti-tumor activity upon detection of a complex array of tumor ligands, but this has not been thoroughly explored in the context of sarcoma immunotherapy. In this study, we investigated the NK cell receptor/ligand immune profile of primary human sarcoma explants. Analysis of tumors from 32 sarcoma patients identified the proliferative marker PCNA and DNAM-1 ligands CD112 and/or CD155 as commonly expressed antigens that could be efficiently targeted by genetically modified (GM) NK cells. Despite the strong expression of CD112 and CD155 on sarcoma cells, characterization of freshly dissociated sarcomas revealed a general decrease in tumor-infiltrating NK cells compared to the periphery, suggesting a defect in the endogenous NK cell response. We also applied a functional screening approach to identify relevant NK cell receptor/ligand interactions that induce efficient anti-tumor responses using a panel NK-92 cell lines GM to over-express 12 different activating receptors. Using GM NK-92 cells against primary sarcoma explants (n = 12) revealed that DNAM-1 over-expression on NK-92 cells led to efficient degranulation against all tested explants (n = 12). Additionally, NKG2D over-expression showed enhanced responses against 10 out of 12 explants. These results show that DNAM-1(+) or NKG2D(+) GM NK-92 cells may be an efficient approach in targeting sarcomas. The degranulation capacity of GM NK-92 cell lines was also tested against various established tumor cell lines, including neuroblastoma, Schwannoma, melanoma, myeloma, leukemia, prostate, pancreatic, colon, and lung cancer. Enhanced degranulation of DNAM-1(+) or NKG2D(+) GM NK-92 cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1(+) or NKG2D(+) GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Georgoudaki, Anna-MariaKarolinska Institutet (författare)
  • Chrobok, MichaelKarolinska Institutet (författare)
  • Ozkazanc, DidemSabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. (författare)
  • Josey, Benjamin J.Nova Southeastern Univ, Dr Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA. (författare)
  • Arif, MuhammadKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1vvaean (författare)
  • Kusser, KimNova Southeastern Univ, Translat Res & Econ Dev, Ft Lauderdale, FL 33314 USA. (författare)
  • Hartman, MichelleNova Southeastern Univ, Translat Res & Econ Dev, Ft Lauderdale, FL 33314 USA. (författare)
  • Chinn, Tamara M.Nova Southeastern Univ, Dr Kiran C Patel Coll Osteopath Med, Ft Lauderdale, FL 33314 USA. (författare)
  • Potens, ReneeNova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA. (författare)
  • Pamukcu, CevriyeSabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. (författare)
  • Krueger, RobinNova Southeastern Univ, Translat Res & Econ Dev, Ft Lauderdale, FL 33314 USA. (författare)
  • Zhang, ChengKings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.(Swepub:kth)u1ww5kvp (författare)
  • Mardinoglu, AdilKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u1t8kmr6 (författare)
  • Alici, EvrenKarolinska Institutet (författare)
  • Temple, Harry ThomasNova Southeastern Univ, Dr Kiran C Patel Coll Allopath Med, Dept Surg, Ft Lauderdale, FL 33314 USA. (författare)
  • Sutlu, TolgaBogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey. (författare)
  • Duru, Adil DoganayNova Southeastern Univ, Dr Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA.;Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden. (författare)
  • Karolinska InstitutetNova Southeastern Univ, Dr Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Frontiers in Immunology: FRONTIERS MEDIA SA111664-3224

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