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Tumor-activated lym...
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma
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- Apollonio, Benedetta (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.;Ist Tumori Giovanni Paolo II, Dept Rare Tumors & Melanoma, Lab Tumor Immunol & Immunotherapy, Viale O Flacco 65, I-70124 Bari, Italy.
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- Spada, Filomena (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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- Petrov, Nedyalko (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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- Cozzetto, Domenico (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Translat Bioinformat, London, England.;Kings Coll London, London, England.;Imperial Coll London, Fac Med, Div Digest Dis, London, England.
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- Papazoglou, Despoina (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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- Jarvis, Peter (författare)
- Aristotle Univ Thessaloniki, Surg Dept 5, Thessaloniki, Greece.
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- Kannambath, Shichina (författare)
- Kings Coll London, London, England.;Guys & St Thomass NHS Fdn Trust, BRC Genom Res Platform, London, England.
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- Terranova-Barberio, Manuela (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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- Amini, Rose-Marie (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Enblad, Gunilla (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Graham, Charlotte (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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- Benjamin, Reuben (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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- Phillips, Elisabeth (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.
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- Ellis, Richard (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England.
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Nuamah, Rosamond (författare)
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- Saqi, Mansoor (författare)
- Guys & St Thomass NHS Fdn Trust, BRC Translat Bioinformat, London, England.;Kings Coll London, London, England.
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- Calado, Dinis P. (författare)
- Francis Crick Inst, Immun & Canc Lab, London, England.
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- Rosenquist, Richard (författare)
- Karolinska Institutet
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- Sutton, Lesley A. (författare)
- Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Salisbury, Jon (författare)
- Kings Coll Hosp NHS Fdn Trust, Dept Haematol, London, England.
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- Zacharioudakis, Georgios (författare)
- Aristotle Univ Thessaloniki, Surg Dept 5, Thessaloniki, Greece.
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- Vardi, Anna (författare)
- G Papanikolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanikolaou Hosp, HCT Unit, Thessaloniki, Greece.
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- Hagner, Patrick R. (författare)
- Bristol Myers Squibb, Summit, NJ USA.
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- Gandhi, Anita K. (författare)
- Bristol Myers Squibb, Summit, NJ USA.
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- Bacac, Marina (författare)
- Roche Innovat Ctr Zurich, Schlieren, Switzerland.
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- Claus, Christina (författare)
- Roche Innovat Ctr Zurich, Schlieren, Switzerland.
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- Umana, Pablo (författare)
- Roche Innovat Ctr Zurich, Schlieren, Switzerland.
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- Jarrett, Ruth F. (författare)
- Univ Glasgow, MRC, Ctr Virus Res, Glasgow, Scotland.
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- Klein, Christian (författare)
- Roche Innovat Ctr Zurich, Schlieren, Switzerland.
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- Deutsch, Alexander (författare)
- Med Univ Graz, Div Hematol, Graz, Austria.
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- Ramsay, Alan G. (författare)
- Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England.;Guys Canc Ctr, Lymphoma Immunol, Innovat Hub, London SE1 9RT, England.
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Kings Coll London, Fac Life Sci & Med, Sch Canc & Pharmaceut Sci, London, England;Ist Tumori Giovanni Paolo II, Dept Rare Tumors & Melanoma, Lab Tumor Immunol & Immunotherapy, Viale O Flacco 65, I-70124 Bari, Italy. Guys & St Thomass NHS Fdn Trust, BRC Adv Cytometry Platform, London, England. (creator_code:org_t)
- American Society for Clinical Investigation, 2023
- 2023
- Engelska.
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:13
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD'+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD'+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Apollonio, Bened ...
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Spada, Filomena
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Petrov, Nedyalko
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Cozzetto, Domeni ...
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Papazoglou, Desp ...
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Jarvis, Peter
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visa fler...
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Kannambath, Shic ...
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Terranova-Barber ...
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Amini, Rose-Mari ...
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Enblad, Gunilla
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Graham, Charlott ...
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Benjamin, Reuben
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Phillips, Elisab ...
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Ellis, Richard
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Nuamah, Rosamond
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Saqi, Mansoor
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Calado, Dinis P.
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Rosenquist, Rich ...
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Sutton, Lesley A ...
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Salisbury, Jon
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Zacharioudakis, ...
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Vardi, Anna
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Hagner, Patrick ...
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Gandhi, Anita K.
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Bacac, Marina
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Claus, Christina
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Umana, Pablo
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Jarrett, Ruth F.
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Klein, Christian
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Deutsch, Alexand ...
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Ramsay, Alan G.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Journal of Clini ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet