Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Depleting tumor-specific Tregs at a single site eradicates disseminated tumors
Aurélien Marabelle, … , Victor Tse, Ronald Levy
Aurélien Marabelle, … , Victor Tse, Ronald Levy
Published May 24, 2013
Citation Information: J Clin Invest. 2013;123(6):2447-2463. https://doi.org/10.1172/JCI64859.
View: Text | PDF | Erratum
Research Article Article has an altmetric score of 50

Depleting tumor-specific Tregs at a single site eradicates disseminated tumors

  • Text
  • PDF
Abstract

Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response.

Authors

Aurélien Marabelle, Holbrook Kohrt, Idit Sagiv-Barfi, Bahareh Ajami, Robert C. Axtell, Gang Zhou, Ranjani Rajapaksa, Michael R. Green, James Torchia, Joshua Brody, Richard Luong, Michael D. Rosenblum, Lawrence Steinman, Hyam I. Levitsky, Victor Tse, Ronald Levy

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 4 7 9 14 20 17 21 21 22 18 24 19 11 1 208
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (18)

Title and authors Publication Year
CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small cell lung cancer
Kipp Weiskopf, Nadine Jahchan, peter Schnorr, Sandra Cristea, Aaron Ring, Roy Maute, Anne Volkmer, Jens-Peter Volkmer, Jie Liu, Jing Shan Lim, Dian Yang, Garrett Seitz, Thuyen Nguyen, Di Wu, Kevin Jude, Heather Guerston, Amira Barkal, Francesca Trapani, Julie George, John Poirier, Eric Gardner, Linde Miles, Elisa de Stanchina, Shane Lofgren, Hannes Vogel, monte winslow, Caroline Dive, Roman Thomas, Charles Rudin, Matt van de Rijn, Ravindra Majeti, K. Christopher Garcia, Irving L. Weissman, Julien Sage
Journal of Clinical Investigation 2016
Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies
AM Monjazeb, MS Kent, SK Grossenbacher, C Mall, AE Zamora, A Mirsoian, M Chen, A Kol, SL Shiao, A Reddy, JR Perks, WT Culp, EE Sparger, RJ Canter, GD Sckisel, WJ Murphy
Clinical cancer research 2016
CTLA-4 limits anti-CD20-mediated tumor regression
Z Ren, J Guo, J Liao, Y Luan, Z Liu, Z Sun, X Liu, Y Liang, H Peng, YX Fu
Clinical cancer research 2016
Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together
GW Jones, DG Hill, SA Jones
Frontiers in immunology 2016
Intratumoral Immunization by p19Arf and Interferon-β Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma
JP Catani, RF Medrano, A Hunger, PD Valle, S Adjemian, DB Zanatta, G Kroemer, E Costanzi-Strauss, BE Strauss
Translational oncology 2016
Combinatorial approach to cancer immunotherapy: strength in numbers
AE Vilgelm, DB Johnson, A Richmond
Journal of leukocyte biology 2016
Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia
Q Zhang, DM Hossain, P Duttagupta, D Moreira, X Zhao, H Won, R Buettner, S Nechaev, M Majka, B Zhang, Q Cai, P Swiderski, YH Kuo, S Forman, G Marcucci, M Kortylewski
Blood 2016
Immunomodulatory antibodies for the treatment of lymphoma: Report on the CALYM Workshop
R Houot, P Gaulard, R Schreiber, I Mellman, O Lambotte, PG Coulie, T Fest, A Korman, R Levy, M Shipp, K Tarte, H Kohrt, A Marabelle, S Ansell, H Watier, A Elsas, A Balakumaran, FA Vargas, SA Quezada, G Salles, D Olive
OncoImmunology 2016
Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too?
JM Ryan, JS Wasser, AJ Adler, AT Vella
Expert Opinion on Biological Therapy 2016
TLR-activated plasmacytoid dendritic cells inhibit breast cancer cell growth in vitro and in vivo
J Wu, S Li, Y Yang, S Zhu, M Zhang, Y Qiao, YJ Liu, J Chen
Oncotarget 2016
The oncolytic peptide LTX-315 overcomes resistance of cancers to immunotherapy with CTLA4 checkpoint blockade
T Yamazaki, JM Pitt, M Vétizou, A Marabelle, C Flores, Ø Rekdal, G Kroemer, L Zitvogel
Cell Death and Differentiation 2016
Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody
C Wang, W Sun, G Wright, AZ Wang, Z Gu
Advanced Materials 2016
Strategies for designing synthetic immune agonists
TY Wu
Immunology 2016
Systemic delivery of chTNT-3/CpG immunoconjugates for immunotherapy in murine solid tumor models
JK Jang, LA Khawli, DC Canter, P Hu, TH Zhu, BW Wu, TE Angell, Z Li, AL Epstein
Cancer Immunology, Immunotherapy 2016
OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential
C Lai, S August, A Albibas, R Behar, SY Cho, ME Polak, J Theaker, AS MacLeod, RR French, MJ Glennie, A Al-Shamkhani, E Healy
Clinical cancer research 2016
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells
M De Simone, A Arrigoni, G Rossetti, P Gruarin, V Ranzani, C Politano, RJ Bonnal, E Provasi, ML Sarnicola, I Panzeri, M Moro, M Crosti, S Mazzara, V Vaira, S Bosari, A Palleschi, L Santambrogio, G Bovo, N Zucchini, M Totis, L Gianotti, G Cesana, RA Perego, N Maroni, AP Ceretti, E Opocher, R De Francesco, J Geginat, HG Stunnenberg, S Abrignani, M Pagani
Immunity 2016
Nutrients and the microenvironment to feed a T cell army
MO Johnson, PJ Siska, DC Contreras, JC Rathmell
Seminars in Immunology 2016
Tumor-directed immunotherapy can generate tumor-specific T cell responses through localized co-stimulation
P Ellmark, SM Mangsbo, C Furebring, P Norlén, TH Tötterman
Cancer Immunology, Immunotherapy 2016

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 3 news outlets
Blogged by 2
Posted by 8 X users
Referenced in 75 patents
On 1 Facebook pages
Referenced in 1 Wikipedia pages
387 readers on Mendeley
See more details