Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance.

Blood
Hisataka KobayashiY Tagaya

Abstract

Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells. Recently, we demonstrated that IL-15Ralpha expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiologic concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Ralpha into a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity, resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore, these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells play an important role in the rejection of MC38 cells under these circumstances. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore, our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis.

References

Mar 15, 1994·International Journal of Cancer. Journal International Du Cancer·T FujiwaraE A Grimm
May 12, 1998·Cellular and Molecular Life Sciences : CMLS·D E Speiser, P S Ohashi
Aug 27, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S Bulfone-PausH Krause
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M K SlifkaJ L Whitton
Mar 8, 2000·The Journal of Experimental Medicine·M K KennedyJ J Peschon
Oct 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·J Marks-KonczalikY Tagaya
Mar 15, 2001·Nature Immunology·P MarrackJ Kappler
Oct 17, 2001·The Journal of Experimental Medicine·J P LodolceA Ma
Mar 20, 2002·Cytokine & Growth Factor Reviews·Todd A FehnigerMichael A Caligiuri
Jun 19, 2002·The Journal of Experimental Medicine·Todd C BeckerRafi Ahmed
Oct 9, 2002·The Journal of Experimental Medicine·Adam D JudgeJonathan Sprent
Oct 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark P RubinsteinDavid J Cole
Nov 16, 2002·Immunity·Sigrid DuboisYutaka Tagaya
Mar 18, 2003·Nature Immunology·Amanda V GettJens Geginat
Apr 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Patrick R BurkettDavid L Boone
May 27, 2003·Nature Reviews. Immunology·Francesco ColucciJames P Di Santo
Jul 30, 2003·Journal of Leukocyte Biology·Jennifer A ToomeyColin G Brooks

❮ Previous
Next ❯

Citations

Mar 5, 2008·Cancer Immunology, Immunotherapy : CII·Karl-Johan MalmbergHans-Gustaf Ljunggren
Jun 25, 2013·Cytokine & Growth Factor Reviews·Danilo PagliariFranco Pandolfi
Apr 23, 2013·Cellular & Molecular Immunology·Min ChengZhigang Tian
Apr 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Meili ZhangThomas A Waldmann
May 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rebecca Berlant LiuBana Jabri
Jan 11, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Eui-Cheol ShinBarbara Rehermann
Jan 18, 2006·Annual Review of Medicine·Thomas A Waldmann
Mar 1, 2012·Cancer Research·Rebecca B LiuHans Schreiber
Jun 10, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Alison L Van DykeAnn G Schwartz
Oct 7, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ping YuThomas A Waldmann
May 25, 2012·PloS One·Katherine C VerbistKimberly D Klonowski
Oct 15, 2011·Immunotherapy·Anshu Malhotra, Anil Shanker
Oct 10, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chuanyu WeiZongliu Hou
Apr 4, 2014·Transgenic Research·Raimund M VielnascherMathias Müller
Aug 11, 2010·Cancer Immunology, Immunotherapy : CII·C J SanchezR T Costello
Mar 23, 2013·Annual Review of Immunology·Eric O LongSumati Rajagopalan
Oct 15, 2014·Médecine sciences : M/S·Erwan MortierSébastien Morisseau
Aug 5, 2009·Critical Reviews in Clinical Laboratory Sciences·Constantin N BaxevanisMichael Papamichail
Jun 24, 2008·Journal of Immunotoxicology·John C MorrisJohn E Janik
Aug 2, 2013·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Baris E DayancElizabeth A Repasky
May 21, 2011·Expert Review of Clinical Immunology·Amy Gillgrass, Ali Ashkar
Feb 7, 2009·Expert Review of Vaccines·Luiz Rodrigues, Cristina Bonorino
Nov 2, 2014·Expert Review of Clinical Immunology·Thomas A Waldmann
Oct 27, 2007·Expert Opinion on Biological Therapy·Jonathan M WeissRobert H Wiltrout
Dec 18, 2007·Expert Opinion on Biological Therapy·Frank Schmitz, Antje Heit
Jan 26, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Monzr M Al MalkiStefan O Ciurea
Oct 13, 2012·Biochemical and Biophysical Research Communications·Yoshio SakaiShuichi Kaneko
Oct 29, 2011·Trends in Pharmacological Sciences·Jason C SteelJohn C Morris
Feb 10, 2009·Veterinary Immunology and Immunopathology·Pei-Chung ChouRea-Min Chu
Aug 14, 2012·Arthritis·Ana Cecilia Machado DiazAlicia Santos Savio

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.