IL10 receptor is a novel therapeutic target in DLBCLs

Leukemia
W BéguelinR Shaknovich

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease with marked genomic instability and variable response to conventional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. More clinically aggressive cases of DLBCLs have high level of circulating interleukin 10 (IL10) cytokine and evidence of activated intracellular STAT3 (signal transducer and activator of transcription 3) signaling. We investigated the role of IL10 and its surface receptor in supporting the neoplastic phenotype of DLBCLs. We determined that IL10RA gene is amplified in 21% and IL10RB gene in 10% of primary DLBCLs. Gene expression of IL10, IL10RA and IL10RB was markedly elevated in DLBCLs. We hypothesized that DLBCLs depend for their proliferation and survival on IL10-STAT3 signaling and that blocking the IL10 receptor (IL10R) would induce cell death. We used anti-IL10R blocking antibody, which resulted in a dose-dependent cell death in all tested activated B-cell-like subtype of DLBCL cell lines and primary DLBCLs. Response of germinal center B-cell-like subtype of DLBCL cell lines to anti-IL10R antibody varied from sensitive to resistant. Cells underwent cell cycle arrest, follo...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·F RoussetJ Banchereau
May 1, 1995·Cellular Immunology·A LichtensteinJ Berenson
Mar 13, 2001·Annual Review of Immunology·K W MooreA O'Garra
Sep 14, 2001·Current Opinion in Oncology·B Coiffier
Jan 5, 2002·Journal of Neuroimmunology·Klemen StrleKeith W Kelley
Jun 21, 2002·The New England Journal of Medicine·Andreas RosenwaldUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Nov 1, 2003·The Journal of Biological Chemistry·Yasuhiro YoshidaPhilip E Auron
Dec 23, 2003·Expert Review of Anticancer Therapy·Yutaka HoriguchiKazuo Umezawa
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Oct 17, 2006·Nature Medicine·David G BrooksMichael B A Oldstone
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rameen BeroukhimWilliam R Sellers
May 1, 2009·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Kunihiro Yamaoka, Yoshiya Tanaka
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gersende CaronThierry Fest
Dec 19, 2009·Blood·Sebastian RutschSiegfried Janz
Jun 3, 2010·Cold Spring Harbor Perspectives in Biology·Louis M Staudt
Sep 18, 2010·Cytokine & Growth Factor Reviews·Alexander Zdanov
Oct 12, 2010·Immunology Letters·Jessica Matesanz-IsabelPablo Engel
Jul 5, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·K Umezawa
Mar 2, 2012·The New England Journal of Medicine·Srdan VerstovsekHagop M Kantarjian
Mar 23, 2012·Immunological Reviews·Kian-Huat LimLouis M Staudt
Jan 12, 2013·Pharmacotherapy·Alex Ganetsky
Apr 10, 2013·Arthritis Research & Therapy·Ioannis KalampokisThomas F Tedder
Oct 3, 2013·Expert Review of Hematology·Claire HarrisonSrdan Verstovsek
Nov 13, 2013·Transplantation Proceedings·I GoodeS T Ildstad

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Citations

Jul 20, 2018·The Journal of Clinical Investigation·Lorena FontánAri Melnick
Nov 20, 2016·Clinical Microbiology Reviews·Carole EldinDidier Raoult
Mar 16, 2019·Immunological Reviews·Coraline MlynarczykAri Melnick
Feb 13, 2020·International Journal of Molecular Sciences·Kiyoharu FukushimaHiroshi Kida
Jan 8, 2019·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Yuki HosokawaKrzysztof M Kuczkowski
Nov 24, 2016·The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG·Ting-Ting Wu, David S Hoff
Nov 27, 2019·Human Vaccines & Immunotherapeutics·C Riccay ElizondoRobert K Bright
Apr 30, 2016·The Journal of Biological Chemistry·Sebastian HörberFrank Essmann
Jul 19, 2019·Frontiers in Oncology·Frédérique LarousserieOdile Devergne
Dec 17, 2020·Chinese Medical Journal·Liang Wang, Lin-Rong Li
May 4, 2021·Blood Research·Yoon Seok Choi
Aug 14, 2021·Tzu Chi Medical Journal·Cheng-Der LiuWei-Han Huang

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