IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs

Cancer Research
Jan EmmerichMartin Oft

Abstract

The presence of activated intratumoral T cells correlates clinically with better prognosis in patients with cancer. Although tumor vaccines can increase the number of tumor-specific CD8(+) T cells in systemic circulation, they frequently fail to increase the number of active and tumor reactive T cells within the tumor. Here we show that treatment with the pleiotropic cytokine interleukin-10 (IL-10) induces specific activation of tumor-resident CD8(+) T cells as well as their intratumoral expansion in several mouse tumor models. We found that inhibition of T-cell trafficking from lymphoid organs did not impair IL-10-induced tumor rejection or the activation of tumor-resident CD8(+) T cells. Tumor-resident CD8(+) T cells expressed elevated levels of the IL-10 receptor and were directly activated by IL-10, resulting in prominent phosphorylation of STAT3 and STAT1. Although CD4(+) T cells, regulatory T cells, NK cells, and dendritic cells have been reported as prominent targets of IL-10 in the tumor microenvironment, we found that expression of the IL-10R was required only on CD8(+) T cells to facilitate IL-10-induced tumor rejection as well as in situ expansion and proliferation of tumor-resident CD8 T cells. Together, our finding...Continue Reading

References

Apr 17, 1996·Journal of the National Cancer Institute·N KunduA M Fulton
Aug 1, 1996·The Journal of Experimental Medicine·L M ZhengI King
Feb 9, 2000·Trends in Pharmacological Sciences·V BrinkmannL Feng
Jul 18, 2000·European Journal of Immunology·A JossC A Akdis
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·F N LauwT van der Poll
Mar 13, 2001·Annual Review of Immunology·K W MooreA O'Garra
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H AsaoK Sugamura
Aug 30, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhi-Ying ChenMark A Kay
Oct 21, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Linda HibbertRobert A Kastelein
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Steven A RosenbergSeth M Steinberg
Dec 24, 2005·The New England Journal of Medicine·Franck PagèsJérôme Galon
May 12, 2006·Nature·John L LangowskiMartin Oft
Aug 19, 2006·Immunological Investigations·Daniel T FisherSharon S Evans
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Partha Sarathi BiswasEric G Pamer
Jul 16, 2008·Seminars in Cell & Developmental Biology·Gabriella RegisValeria Poli
Aug 13, 2008·Expert Opinion on Biological Therapy·David J Andorsky, John M Timmerman
Oct 5, 2010·Clinical & Developmental Immunology·Mingli XuTakayuki Yoshimoto
Jan 12, 2011·Immunology and Cell Biology·Joanna R Groom, Andrew D Luster
Apr 14, 2011·Experimental Biology and Medicine·Caroline Jochems, Jeffrey Schlom
Dec 17, 2011·Cancer Cell·John B MummMartin Oft

❮ Previous
Next ❯

Citations

Oct 11, 2014·The Journal of Investigative Dermatology·Terry R Medler, Lisa M Coussens
Mar 26, 2014·Expert Opinion on Biological Therapy·Belal ChaudharyEyad Elkord
Jan 8, 2013·Expert Opinion on Biological Therapy·Constantin N BaxevanisSonia A Perez
Dec 3, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Sojan AbrahamPremlata Shankar
Aug 27, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ivan Ho ChanJohn Brian Mumm
Mar 17, 2016·Cytokine & Growth Factor Reviews·Jens GeginatRichard A Flavell
May 15, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·John B Mumm, Martin Oft
Jun 2, 2015·Immunity, Inflammation and Disease·Evgeniya V ShmelevaIoakim Spyridopoulos
Jan 16, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Agung Endro NugrohoEdy Meiyanto
Jul 19, 2015·Cancer Letters·Mark H ManninoYujiang Fang
Jan 12, 2013·Trends in Molecular Medicine·Gopal Murugaiyan, Bhaskar Saha
Jul 30, 2014·Cell Reports·Michelle ElvingtonStephen Tomlinson
Jan 18, 2015·Cellular Immunology·Guoying NiXiaosong Liu
Sep 3, 2016·Developmental and Comparative Immunology·M Carla PiazzonMaria Forlenza
Oct 13, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li LiXin-Yan Xu
Aug 17, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Aung NaingJeffrey R Infante
Aug 31, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hui ZhangYou-Wen He
May 4, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jianfeng DongDawei Wang
Feb 27, 2018·Cancer Immunology, Immunotherapy : CII·Guang ShanYue Xia
Nov 22, 2017·Journal for Immunotherapy of Cancer·Adam Ajina, John Maher
Sep 6, 2017·Cancer Immunology, Immunotherapy : CII·Sotirios P FortisConstantin N Baxevanis
Sep 28, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qingsheng LiNejat K Egilmez
Oct 6, 2018·Cell Biology International·Fereshteh MehdipourAbbas Ghaderi
Oct 30, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas Powles, Brian Rini
Jun 8, 2019·Expert Opinion on Biological Therapy·Iris Y Sheng, Brian I Rini
Sep 5, 2019·Cancers·Cédric Rébé, François Ghiringhelli
Oct 16, 2019·The Journal of Experimental Medicine·Margarida SaraivaAnne O'Garra

❮ 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.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.