Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells.

Cancer Research
Mathieu EpardaudShannon J Turley

Abstract

Tumors often escape immune-mediated destruction by suppressing lymphocyte infiltration or effector function. New approaches are needed that overcome this suppression and thereby augment the tumoricidal capacity of tumor-reactive lymphocytes. The cytokine interleukin-15 (IL-15) promotes proliferation and effector capacity of CD8(+) T cells, natural killer (NK) cells, and NKT cells; however, it has a short half-life and high doses are needed to achieve functional responses in vivo. The biological activity of IL-15 can be dramatically increased by complexing this cytokine to its soluble receptor, IL-15R alpha. Here, we report that in vivo delivery of IL-15/IL-15R alpha complexes triggers rapid and significant regression of established solid tumors in two murine models. Despite a marked expansion of IL-2/IL-15R beta(+) cells in lymphoid organs and peripheral blood following treatment with IL-15/IL-15R alpha complexes, the destruction of solid tumors was orchestrated by tumor-resident rather than newly infiltrating CD8(+) T cells. Our data provide novel insights into the use of IL-15/IL-15R alpha complexes to relieve tumor-resident T cells from functional suppression by the tumor microenvironment and have significant implications fo...Continue Reading

Citations

Sep 28, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Nejat K Egilmez, Mehmet O Kilinc
Feb 15, 2012·Cancer Immunology, Immunotherapy : CII·Ute E BurkhardtWinfried S Wels
Oct 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Grégory VerdeilLinda A Sherman
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hirotsugu SuwanaiChristophe Benoist
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kutlu G ElpekShannon J Turley
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicholas D HuntingtonJames P Di Santo
May 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rebecca Berlant LiuBana Jabri
Dec 24, 2010·Protein Engineering, Design & Selection : PEDS·Richard L WongHing C Wong
Mar 1, 2012·Cancer Research·Rebecca B LiuHans Schreiber
Nov 15, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Serena K PernaBarbara Savoldo
Jul 17, 2009·Blood·Carolina BergerStanley R Riddell
Nov 3, 2012·PloS One·Elisenda Alari-PahissaPilar Lauzurica
Sep 11, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Dafne Müller
Apr 9, 2014·Cancer Immunology, Immunotherapy : CII·Britnie R JamesThomas S Griffith
Feb 12, 2010·Expert Opinion on Biological Therapy·Miriam CoccorisReno Debets
Jul 16, 2015·International Journal of Cancer. Journal International Du Cancer·Dimitrios MathiosMichael Lim
Sep 18, 2012·Cytokine & Growth Factor Reviews·Julien Giron-MichelBruno Azzarone
Jul 15, 2015·Journal of Zhejiang University. Science. B·Hui-ying WangXin-guo Jiang
Mar 3, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Dong TangKuirong Jiang
Sep 26, 2015·Oncoimmunology·Rajia BahriSilvia Bulfone-Paus
Dec 4, 2013·FEBS Letters·Mahiuddin Ahmed, Nai-Kong V Cheung
Mar 28, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Robert SacksteinSteven R Barthel
Apr 15, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xilong WuXuesi Chen
Jun 12, 2010·Journal of Leukocyte Biology·Elizabeth DaviesAli A Ashkar
Nov 11, 2008·Oral Diseases·E HannaS K Libutti
Jul 6, 2014·Nature Reviews. Cancer·Brian D LichtyJohn C Bell
May 21, 2011·Expert Review of Clinical Immunology·Amy Gillgrass, Ali Ashkar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

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.