IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation

European Journal of Immunology
Christian M HüberFrancesco Colucci

Abstract

Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus host disease (GvHD). Here, we show that adoptively transferred IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor T cells or host DCs by the IL-12/15/18-preactivated NK cells, proliferation of donor T cells was inhibited. Strikingly, the graft versus leukemia effect mediated by donor T cells was retained, resulting in improved overall survival of mice that received lymphoma cells, donor allogeneic T cells, and IL-12/15/18-preactivated NK cells. These results suggest that IL-12/15/18-preactivated NK cells may be useful in improving immunotherapy of mismatched hematopoietic cell transplantation. Compared with previously proposed protocols, our findings suggest that in vitro NK-cell preactivation with this cytokine cocktail offers the significant advantage that cytokines do not need to be administered systemically to sustain NK-cell activity, thus avoiding toxicity.

References

Dec 14, 1999·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·M Ito, J A Shizuru
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian A RabinovichRichard G Miller
Apr 18, 2006·Nature Immunology·Jacqueline G O'LearyUlrich H von Andrian
Jan 13, 2009·Nature·Joseph C SunLewis L Lanier
Feb 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Megan A CooperWayne M Yokoyama
Oct 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew A SmithKenneth L Wright
Dec 2, 2011·The New England Journal of Medicine·John KorethRobert J Soiffer
Aug 14, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seung-Hwan LeeChristine A Biron
Sep 18, 2012·Blood·Rizwan RomeeTodd A Fehniger
Dec 5, 2012·The Journal of Experimental Medicine·Jing NiAdelheid Cerwenka
Mar 27, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Molly P KeppelMegan A Cooper
Jan 18, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jeffrey W LeongTodd A Fehniger

❮ Previous
Next ❯

Citations

Jan 26, 2016·Nature Reviews. Immunology·Adelheid Cerwenka, Lewis L Lanier
Jul 6, 2016·Frontiers in Immunology·Federico SimonettaEddy Roosnek
Oct 28, 2016·Frontiers in Immunology·Yuhao JiaoCyril Seillet
May 11, 2017·Frontiers in Immunology·Federico SimonettaRobert S Negrin
Mar 24, 2016·Journal of Leukocyte Biology·Allison M Felker, B Anne Croy
Aug 9, 2020·Molecular Cancer·Song-Yang WuZhi-Ming Shao
Mar 21, 2021·Scientific Reports·Iñigo TerrénFrancisco Borrego

❮ Previous
Next ❯

Methods Mentioned

BETA
PMA
flow cytometry

Software Mentioned

FlowJo
GraphPad Prism
BD FACS Diva

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.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.