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: 5 7 9 14 20 17 21 21 22 18 24 19 11 1 209
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 2014 (19)

Title and authors Publication Year
Development and Characterization of a Preclinical Model of Breast Cancer Lung Micrometastatic to Macrometastatic Progression
LC Bailey-Downs, JE Thorpe, BC Disch, A Bastian, PJ Hauser, T Farasyn, WL Berry, RE Hurst, MA Ihnat, A Angelucci
PloS one 2014
Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer
D Zamarin, JD Wolchok
Molecular Therapy — Oncolytics 2014
Localized Oncolytic Virotherapy Overcomes Systemic Tumor Resistance to Immune Checkpoint Blockade Immunotherapy
D Zamarin, RB Holmgaard, SK Subudhi, JS Park, M Mansour, P Palese, T Merghoub, JD Wolchok, JP Allison
Science Translational Medicine 2014
The "Trojan Horse" Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
D Nelson, S Fisher, B Robinson
Journal of Immunology Research 2014
Intratumoral Immunization: A New Paradigm for Cancer Therapy
A Marabelle, H Kohrt, C Caux, R Levy
Clinical cancer research 2014
Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial
JR Westin, F Chu, M Zhang, LE Fayad, LW Kwak, N Fowler, J Romaguera, F Hagemeister, M Fanale, F Samaniego, L Feng, V Baladandayuthapani, Z Wang, W Ma, Y Gao, M Wallace, LM Vence, L Radvanyi, T Muzzafar, R Rotem-Yehudar, RE Davis, SS Neelapu
The Lancet Oncology 2014
A brief personal history of cancer immunotherapy at Stanford: if these walls could talk…
R Levy
Immunologic Research 2014
Intraperitoneal prophylaxis with CpG oligodeoxynucleotides protects neutropenic mice against intracerebral Escherichia coli K1 infection
S Ribes, T Meister, M Ott, S Redlich, H Janova, UK Hanisch, S Nessler, R Nau
Journal of Neuroinflammation 2014
New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape
D Mittal, MM Gubin, RD Schreiber, MJ Smyth
Current Opinion in Immunology 2014
Intratumoral checkpoint subversion as a strategy for minimizing adverse effects: Harvesting the power of TILs without harvesting TILs
L Alabanza, S Gnjatic, N Bhardwaj, J Brody
OncoImmunology 2014
Combined OX40 ligation plus CTLA-4 blockade: More than the sum of its parts
SN Linch, WL Redmond
OncoImmunology 2014
How Do CD4(+) T Cells Detect and Eliminate Tumor Cells That Either Lack or Express MHC Class II Molecules?
OA Haabeth, AA Tveita, M Fauskanger, F Schjesvold, KB Lorvik, PO Hofgaard, H Omholt, LA Munthe, Z Dembic, A Corthay, B Bogen
Frontiers in immunology 2014
New insights into the mechanism of action of immune checkpoint antibodies
A Marabelle, H Kohrt, R Levy
OncoImmunology 2014
Immunomodulatory Antibody Therapy of Cancer: The Closer, the Better
RS Dronca, H Dong
Clinical cancer research 2014
The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40
A Khong, AL Cleaver, MF Alatas, BC Wylie, T Connor, SA Fisher, S Broomfield, WJ Lesterhuis, AJ Currie, RA Lake, BW Robinson
BMC Cancer 2014
CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1
P Yin, X Liu, AS Mansfield, SM Harrington, Y Li, Y Yan, H Dong
Oncotarget 2014
The early history of Stanford Immunology
PP Jones, LA Herzenberg
Immunologic Research 2014
Targeting the tumor microenvironment to enhance antitumor immune responses
Van der Jeught K, Bialkowski L, Daszkiewicz L, Broos K, Goyvaerts C, Renmans D, Van Lint S, Heirman C, Thielemans K, Breckpot K
Oncotarget 2014
Cryoimmunotherapy with local co-administration of ex vivo generated dendritic cells and CpG-ODN immune adjuvant, elicits a specific antitumor immunity.
Alteber Z, Azulay M, Cafri G, Vadai E, Tzehoval E, Eisenbach L
Cancer Immunology, Immunotherapy 2014

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