Mammary-tumor-educated B cells acquire LAP/TGF-β and PD-L1 expression and suppress anti-tumor immune responses

International Immunology
Yu ZhangJoseph D Rosenblatt

Abstract

B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild-type (WT) mice but show reduced growth in B-cell-deficient μ(-/-) BALB/c mice (BCDM). WT mice demonstrate extensive B-cell infiltration into the tumor bed, reduced CD8(+) T cell and CD49(+) NK cell infiltration, and markedly reduced cytolytic T-cell response relative to BCDM. Expression of LAP/TGF-β1, CD80, CD86 and PD-L1 is significantly increased in tumor-infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-β1 expression on TIL-B progressively increased from 5.4±1.7% on day 8 to 43.1±6.1% by day 21 post tumor implantation. Co-culture of EMT-6 tumor cells with Naive-B cells ex vivo generated B cells (EMT6-B) with a similar immunophenotype to TIL-B. Purified TIL-B, or in-vitro-generated EMT6-B suppressed CD4(+), CD8(+) and CD4(+)CD25(-) T-cell proliferation, and Th1 cytokine secretion, and also suppressed purified NK-cell proliferation in response to IL-15, compared to naive splenic B cells. Acquired B regulatory function required direct tumor cell: B-cell contact, and was partially reversed by antibody to TGF-β or PD-L1, leading to tumor rej...Continue Reading

References

May 19, 1998·Nature Medicine·Z QinT Blankenstein
Apr 28, 2000·International Immunology·E MizoguchiA K Bhan
Sep 24, 2002·Nature Immunology·Simon FillatreauStephen M Anderton
May 17, 2005·Cancer Cell·Karin E de VisserLisa M Coussens
May 25, 2005·International Journal of Cancer. Journal International Du Cancer·Sangeeta ShahJoseph D Rosenblatt
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·David P HarrisFrances E Lund
Aug 4, 2006·Cancer Research·Satoshi InoueDorothy Scott
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monica K MannBonnie N Dittel
Jul 11, 2008·Immunological Reviews·Koichi YanabaThomas F Tedder
Sep 2, 2008·Immunological Reviews·Jean-David BouazizThomas F Tedder
Sep 20, 2008·The Journal of Clinical Investigation·Takashi MatsushitaThomas F Tedder
Sep 18, 2009·Annals of the New York Academy of Sciences·Sébastien LemoineChristophe Jamin
Feb 12, 2010·Annals of the New York Academy of Sciences·David J DiLilloThomas F Tedder
Mar 12, 2010·Nature·Massimo AmmiranteMichael Karin
Mar 23, 2010·The Journal of Allergy and Clinical Immunology·Sylvie AmuPadraic G Fallon
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rei WatanabeManabu Fujimoto
Jul 14, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takashi MatsushitaThomas F Tedder
Sep 14, 2010·Journal of Dermatological Science·Manabu Fujimoto
Sep 22, 2010·Nature Reviews. Rheumatology·Claudia Mauri, Paul A Blair
Oct 14, 2010·Methods in Molecular Biology·Takashi Matsushita, Thomas F Tedder
Jul 10, 2012·Cancer Immunology, Immunotherapy : CII·Yu ZhangJoseph D Rosenblatt
Jul 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anusha-Preethi GanesanLisa M Coussens
Dec 3, 2013·Immunologic Research·Yu ZhangJoseph Rosenblatt

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Citations

Jun 12, 2016·Journal of Translational Medicine·Woo Young SunJa Seung Koo
Apr 1, 2017·Cancer Immunology, Immunotherapy : CII·Marek K JaniakEdward J Calabrese
Mar 11, 2017·Targeted Oncology·Nicole J FlynnJennifer Sims-Mourtada
Jul 8, 2018·International Journal of Cancer. Journal International Du Cancer·Xiaoyang HouYanqun Liu
Sep 6, 2018·International Journal of Cancer. Journal International Du Cancer·Min LiuXiubao Ren
Mar 4, 2018·HNO·P J SchulerT K Hoffmann
Jun 20, 2017·Cellular & Molecular Immunology·Anushruti SarvariaAurore Saudemont
Jun 30, 2019·Cancers·Prachi GuptaSunila Pradeep
Apr 6, 2020·Clinical and Experimental Pharmacology & Physiology·Da-Nian TongZun-Qiang Zhou
Jun 23, 2016·Oncotarget·Meng ShenXiubao Ren
Nov 26, 2019·Oncotarget·María José Godoy-CalderónAna Federica Convit
Aug 2, 2017·Science Immunology·Galina GabrielyHoward L Weiner
Feb 14, 2019·Scientific Reports·Emma BrännAlkistis Skalkidou
Oct 21, 2019·International Immunology·Yoshihiro BabaYasuaki Kotetsu
Sep 6, 2017·Archives of Pharmacal Research·Hwan Hee LeeHyosun Cho
Jan 7, 2020·Cancer Immunology, Immunotherapy : CII·Akshay J PatelGary W Middleton
Mar 7, 2017·Frontiers in Immunology·Ruth Marian Guzman-Genuino, Kerrilyn R Diener
Jun 24, 2017·Journal of Immunology Research·Wuzhen ChenJian Huang
Oct 30, 2020·Cancers·Vivian Weiwen XuePatrick Ming-Kuen Tang
Jun 21, 2019·American Journal of Therapeutics·Kim Phan, Mahmoud Charif
Mar 22, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hope S RugoAntoinette R Tan
Jan 8, 2021·Immunological Reviews·Madhvi MenonHalima Ali Shuwa
Jan 27, 2021·Cancers·Faustino Julián Suárez-SánchezJuan Carlos de Vicente
Nov 17, 2020·Frontiers in Immunology·Jin ShangYufa Sun
Dec 29, 2020·Immunological Reviews·Daniel MichaudYuliya Pylayeva-Gupta
Aug 22, 2020·Life Sciences·Parisa LotfinejadBehzad Baradaran
Apr 6, 2021·Clinical & Translational Immunology·Guoli HuaiCharles Gerard Rickert
Aug 1, 2020·Gynecologic Oncology·Adrien CrestaniJennifer Pasquier
Apr 17, 2021·International Immunopharmacology·Huan-Rong LanXue Yang
Dec 21, 2018·International Immunopharmacology·Xiaoyu CaiWei Wei
May 18, 2021·Frontiers in Immunology·Diego CatalánOctavio Aravena
Jun 1, 2021·Frontiers in Immunology·Jessica N FildermanWalter J Storkus

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