Journal Article
. 2013 Jun; 123(6):2447-63.
doi: 10.1172/JCI64859.

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

Aurélien Marabelle 1 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  
Affiliations
  • PMID: 23728179
  •     59 References
  •     169 citations

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.

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Arta M Monjazeb, Michael S Kent, +13 authors, William J Murphy.
Clin Cancer Res, 2016 Mar 17; 22(17). PMID: 26979392    Free PMC article.
OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.
Chester Lai, Suzannah August, +9 authors, Eugene Healy.
Clin Cancer Res, 2016 Apr 02; 22(16). PMID: 27034329    Free PMC article.
The oncolytic peptide LTX-315 overcomes resistance of cancers to immunotherapy with CTLA4 checkpoint blockade.
T Yamazaki, J M Pitt, +5 authors, L Zitvogel.
Cell Death Differ, 2016 Apr 16; 23(6). PMID: 27082453    Free PMC article.
Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer.
Dmitriy Zamarin, Jedd D Wolchok.
Mol Ther Oncolytics, 2014 Jan 01; 1. PMID: 27119094    Free PMC article.
Review.
Strategies for designing synthetic immune agonists.
Tom Y-H Wu.
Immunology, 2016 May 24; 148(4). PMID: 27213842    Free PMC article.
Review.
CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer.
Kipp Weiskopf, Nadine S Jahchan, +31 authors, Julien Sage.
J Clin Invest, 2016 Jun 14; 126(7). PMID: 27294525    Free PMC article.
Highly Cited.
CTLA-4 Limits Anti-CD20-Mediated Tumor Regression.
Zhenhua Ren, Jingya Guo, +7 authors, Yang-Xin Fu.
Clin Cancer Res, 2016 Jun 30; 23(1). PMID: 27354469    Free PMC article.
Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody.
Chao Wang, Wujin Sun, +2 authors, Zhen Gu.
Adv Mater, 2016 Oct 21; 28(40). PMID: 27558441    Free PMC article.
CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1.
Peng Yin, Xin Liu, +4 authors, Haidong Dong.
Oncotarget, 2016 Sep 08; 7(43). PMID: 27602959    Free PMC article.
Immunomodulatory antibodies for the treatment of lymphoma: Report on the CALYM Workshop.
Roch Houot, Philippe Gaulard, +18 authors, Daniel Olive.
Oncoimmunology, 2016 Sep 14; 5(7). PMID: 27622041    Free PMC article.
Nutrients and the microenvironment to feed a T cell army.
Marc O Johnson, Peter J Siska, Diana C Contreras, Jeffrey C Rathmell.
Semin Immunol, 2016 Oct 08; 28(5). PMID: 27712958    Free PMC article.
Review.
Tumor-directed immunotherapy can generate tumor-specific T cell responses through localized co-stimulation.
Peter Ellmark, Sara M Mangsbo, +2 authors, Thomas H Tötterman.
Cancer Immunol Immunother, 2016 Oct 08; 66(1). PMID: 27714433    Free PMC article.
Review.
Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together.
Gareth W Jones, David G Hill, Simon A Jones.
Front Immunol, 2016 Oct 19; 7. PMID: 27752256    Free PMC article.
Review.
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.
Marco De Simone, Alberto Arrigoni, +28 authors, Massimiliano Pagani.
Immunity, 2016 Nov 17; 45(5). PMID: 27851914    Free PMC article.
Highly Cited.
Intratumoral Immunization by p19Arf and Interferon-β Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma.
João Paulo Portela Catani, Ruan F V Medrano, +6 authors, Bryan E Strauss.
Transl Oncol, 2016 Dec 06; 9(6). PMID: 27916291    Free PMC article.
TLR-activated plasmacytoid dendritic cells inhibit breast cancer cell growth in vitro and in vivo.
Jing Wu, Shuang Li, +5 authors, Jingtao Chen.
Oncotarget, 2017 Jan 05; 8(7). PMID: 28052019    Free PMC article.
Effective Combination of Innate and Adaptive Immunotherapeutic Approaches in a Mouse Melanoma Model.
Alexander L Rakhmilevich, Mildred Felder, +8 authors, Paul M Sondel.
J Immunol, 2017 Jan 08; 198(4). PMID: 28062694    Free PMC article.
Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?
Franck Carbonnel, Emilie Soularue, +4 authors, Caroline Robert.
Semin Immunopathol, 2017 Jan 18; 39(3). PMID: 28093620
Review.
Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma.
Xiaoyan Feng, Li Zhang, +6 authors, Kenneth C Anderson.
Clin Cancer Res, 2017 Mar 03; 23(15). PMID: 28249894    Free PMC article.
Highly Cited.
Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols.
Matthew T Silvestrini, Elizabeth S Ingham, +12 authors, Katherine W Ferrara.
JCI Insight, 2017 Mar 30; 2(6). PMID: 28352658    Free PMC article.
Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis.
Desislava Tsoneva, Boris Minev, +3 authors, Aladar A Szalay.
Mol Ther Oncolytics, 2017 May 10; 5. PMID: 28480327    Free PMC article.
Intratumoral depletion of regulatory T cells using CD25-targeted photodynamic therapy in a mouse melanoma model induces antitumoral immune responses.
Dong Sun Oh, Heegon Kim, +4 authors, Heung Kyu Lee.
Oncotarget, 2017 May 26; 8(29). PMID: 28537894    Free PMC article.
Delivering safer immunotherapies for cancer.
Lauren Milling, Yuan Zhang, Darrell J Irvine.
Adv Drug Deliv Rev, 2017 May 27; 114. PMID: 28545888    Free PMC article.
Highly Cited. Review.
Intratumoral STING Activation with T-cell Checkpoint Modulation Generates Systemic Antitumor Immunity.
Casey R Ager, Matthew J Reilley, +3 authors, Michael A Curran.
Cancer Immunol Res, 2017 Jul 05; 5(8). PMID: 28674082    Free PMC article.
Highly Cited.
TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.
Timothy Nj Bullock.
Curr Opin Immunol, 2017 Jul 28; 47. PMID: 28750279    Free PMC article.
Review.
Combining dendritic cells and B cells for presentation of oxidised tumour antigens to CD8+ T cells.
Melanie L Grant, Nicholas Shields, +5 authors, Sarah L Young.
Clin Transl Immunology, 2017 Aug 10; 6(7). PMID: 28791124    Free PMC article.
Clinical Applications of Immunotherapy Combination Methods and New Opportunities for the Future.
Ece Esin.
Biomed Res Int, 2017 Aug 30; 2017. PMID: 28848761    Free PMC article.
Review.
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.
David J Messenheimer, Shawn M Jensen, +6 authors, Bernard A Fox.
Clin Cancer Res, 2017 Sep 01; 23(20). PMID: 28855348    Free PMC article.
Highly Cited.
Exploring Synergy in Combinations of Tumor-Derived Vaccines That Harbor 4-1BBL, OX40L, and GM-CSF.
Andrea J Manrique-Rincón, Camila M Beraldo, Jessica M Toscaro, Marcio C Bajgelman.
Front Immunol, 2017 Oct 05; 8. PMID: 28974950    Free PMC article.
STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC.
Qiuju Han, Yaqun Wang, Min Pang, Jian Zhang.
J Exp Clin Cancer Res, 2017 Nov 09; 36(1). PMID: 29115974    Free PMC article.
Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.
Manisha Singh, Christina Vianden, +15 authors, Willem W Overwijk.
Nat Commun, 2017 Nov 14; 8(1). PMID: 29129918    Free PMC article.
Advances in immunotherapeutic research for glioma therapy.
Jeremy Tetsuo Miyauchi, Stella E Tsirka.
J Neurol, 2017 Dec 07; 265(4). PMID: 29209782    Free PMC article.
Review.
The Future of Immunotherapy: A 20-Year Perspective.
David C Wraith.
Front Immunol, 2017 Dec 14; 8. PMID: 29234325    Free PMC article.
Potential effect of tumor-specific Treg-targeted antibodies in the treatment of human cancers: A bioinformatics analysis.
Luigi Cari, Giuseppe Nocentini, Graziella Migliorati, Carlo Riccardi.
Oncoimmunology, 2018 Jan 09; 7(2). PMID: 29308313    Free PMC article.
Eradication of spontaneous malignancy by local immunotherapy.
Idit Sagiv-Barfi, Debra K Czerwinski, +4 authors, Ronald Levy.
Sci Transl Med, 2018 Feb 02; 10(426). PMID: 29386357    Free PMC article.
Highly Cited.
Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking.
Anna H Turaj, Kerry L Cox, +10 authors, Sean H Lim.
Sci Rep, 2018 Feb 06; 8(1). PMID: 29396470    Free PMC article.
Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models.
Grammatiki Fotaki, Chuan Jin, +5 authors, Magnus Essand.
Oncoimmunology, 2018 Feb 06; 7(3). PMID: 29399398    Free PMC article.
A safe and highly efficient tumor-targeted type I interferon immunotherapy depends on the tumor microenvironment.
Anje Cauwels, Sandra Van Lint, +11 authors, Jan Tavernier.
Oncoimmunology, 2018 Feb 06; 7(3). PMID: 29399401    Free PMC article.
B Cell Lymphoma Immunotherapy Using TLR9-Targeted Oligonucleotide STAT3 Inhibitors.
Xingli Zhao, Zhuoran Zhang, +11 authors, Marcin Kortylewski.
Mol Ther, 2018 Feb 13; 26(3). PMID: 29433938    Free PMC article.
Using immunotherapy to boost the abscopal effect.
Wilfred Ngwa, Omoruyi Credit Irabor, +3 authors, Silvia C Formenti.
Nat Rev Cancer, 2018 Feb 17; 18(5). PMID: 29449659    Free PMC article.
Highly Cited. Review.
Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression.
Yawara Kawano, Oksana Zavidij, +24 authors, Irene M Ghobrial.
J Clin Invest, 2018 Mar 21; 128(6). PMID: 29558366    Free PMC article.
Anti-CTLA-4 immunotherapy: uncoupling toxicity and efficacy.
Jonathan Pol, Guido Kroemer.
Cell Res, 2018 Mar 30; 28(5). PMID: 29593340    Free PMC article.
Imaging activated T cells predicts response to cancer vaccines.
Israt S Alam, Aaron T Mayer, +7 authors, Sanjiv S Gambhir.
J Clin Invest, 2018 Mar 30; 128(6). PMID: 29596062    Free PMC article.
Highly Cited.
Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody.
Randi B Gombos, Ana Gonzalez, +24 authors, Nicholas S Wilson.
PLoS One, 2018 Apr 05; 13(4). PMID: 29617360    Free PMC article.
CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols.
Jai Woong Seo, Richard Tavaré, +7 authors, Katherine W Ferrara.
Clin Cancer Res, 2018 Jul 04; 24(20). PMID: 29967252    Free PMC article.
Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.
Michael Chavez, Matthew T Silvestrini, +11 authors, Katherine W Ferrara.
Theranostics, 2018 Jul 22; 8(13). PMID: 30026870    Free PMC article.
In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma.
Matthew J Frank, Patrick M Reagan, +9 authors, Ronald Levy.
Cancer Discov, 2018 Aug 30; 8(10). PMID: 30154192    Free PMC article.
A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.
Prabhakaran Kumar, Palash Bhattacharya, Bellur S Prabhakar.
J Autoimmun, 2018 Sep 04; 95. PMID: 30174217    Free PMC article.
Review.
Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide.
Marco C Merlano, Anna M Merlotti, +9 authors, Renzo Corvò.
Clin Transl Radiat Oncol, 2018 Sep 07; 12. PMID: 30186977    Free PMC article.
mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice.
Ole A W Haabeth, Timothy R Blake, +3 authors, Ronald Levy.
Proc Natl Acad Sci U S A, 2018 Sep 12; 115(39). PMID: 30201728    Free PMC article.
Combination immune checkpoint blockade as an effective therapy for mesothelioma.
Vanessa S Fear, Caitlin Tilsed, +10 authors, Scott A Fisher.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288361    Free PMC article.
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity.
David A Knorr, Rony Dahan, Jeffrey V Ravetch.
Proc Natl Acad Sci U S A, 2018 Oct 10; 115(43). PMID: 30297432    Free PMC article.
Effects of tumor metabolic microenvironment on regulatory T cells.
Yi-An Wang, Xiao-Ling Li, +13 authors, Wei Xiong.
Mol Cancer, 2018 Nov 28; 17(1). PMID: 30477520    Free PMC article.
Review.
Immunomodulatory Drugs Encoded by Oncolytic Viruses: Is the Whole Greater Than the Sum?
Dmitriy Zamarin.
Mol Ther, 2019 Oct 07; 27(11). PMID: 31586519    Free PMC article.
Foxp3 Post-translational Modifications and Treg Suppressive Activity.
Guoping Deng, Xiaomin Song, +3 authors, Mark I Greene.
Front Immunol, 2019 Nov 05; 10. PMID: 31681337    Free PMC article.
Review.
TLR9 activation cooperates with T cell checkpoint blockade to regress poorly immunogenic melanoma.
Matthew J Reilley, Brittany Morrow, +3 authors, Michael A Curran.
J Immunother Cancer, 2019 Nov 28; 7(1). PMID: 31771649    Free PMC article.
Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.
Lefu Huang, Guoliang Qiao, +6 authors, Herbert K Lyerly.
Oncol Lett, 2019 Dec 04; 18(6). PMID: 31788044    Free PMC article.
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development.
Amy Li, Rebecca H Herbst, +15 authors, Tyler Jacks.
Cell Rep, 2019 Dec 05; 29(10). PMID: 31801068    Free PMC article.
CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.
Haiping Wang, Fabien Franco, +17 authors, Ping-Chih Ho.
Nat Immunol, 2020 Feb 19; 21(3). PMID: 32066953    Free PMC article.
Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery.
Kenta Narumi, Reina Miyakawa, +7 authors, Kazunori Aoki.
Sci Rep, 2019 Apr 05; 9(1). PMID: 30944344    Free PMC article.
TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing intratumoral Treg depletion.
Naveen Sharma, Jean Vacher, James P Allison.
Proc Natl Acad Sci U S A, 2019 May 12; 116(21). PMID: 31076558    Free PMC article.
APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications.
Yu-Tzu Tai, Liang Lin, +10 authors, Kenneth C Anderson.
Leukemia, 2018 Aug 24; 33(2). PMID: 30135465    Free PMC article.
Intratumoral delivery of antigen with complement C3-bound liposomes reduces tumor growth in mice.
Alexandra Francian, Shelby Namen, +3 authors, Max Kullberg.
Nanomedicine, 2018 Nov 13; 18. PMID: 30419362    Free PMC article.
Local Delivery of Ox40l, Cd80, and Cd86 mRNA Kindles Global Anticancer Immunity.
Ole Audun Werner Haabeth, Timothy R Blake, +5 authors, Ronald Levy.
Cancer Res, 2019 Jan 30; 79(7). PMID: 30692215    Free PMC article.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers-Response.
Anu Sharma, Sumit K Subudhi, +5 authors, Padmanee Sharma.
Clin Cancer Res, 2019 Jun 05; 25(11). PMID: 31160495    Free PMC article.
PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity.
Martin W LaFleur, Thao H Nguyen, +9 authors, Arlene H Sharpe.
Nat Immunol, 2019 Sep 19; 20(10). PMID: 31527834    Free PMC article.
Development and characterization of mammary intraductal (MIND) spontaneous metastasis models for triple-negative breast cancer in syngeneic mice.
Xu-Liang Luo, Lan Lin, +5 authors, Yuan-Qiao He.
Sci Rep, 2020 Mar 15; 10(1). PMID: 32170125    Free PMC article.
Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment.
Heidi Harjunpää, Marc Llort Asens, Carla Guenther, Susanna C Fagerholm.
Front Immunol, 2019 Jun 25; 10. PMID: 31231358    Free PMC article.
Highly Cited. Review.
Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB.
Ingrid Teige, Linda Mårtensson, Björn L Frendéus.
Front Immunol, 2019 Apr 02; 10. PMID: 30930905    Free PMC article.
Review.
Tumor Targeted Nanocarriers for Immunotherapy.
Alejandro Baeza.
Molecules, 2020 Apr 01; 25(7). PMID: 32225049    Free PMC article.
Review.
New pathways in immune stimulation: targeting OX40.
Carolina Alves Costa Silva, Francesco Facchinetti, Bertrand Routy, Lisa Derosa.
ESMO Open, 2020 May 12; 5(1). PMID: 32392177    Free PMC article.
Immune-checkpoint molecules on regulatory T-cells as a potential therapeutic target in head and neck squamous cell cancers.
Susumu Suzuki, Tetsuya Ogawa, +7 authors, Toyonori Tsuzuki.
Cancer Sci, 2020 Apr 19; 111(6). PMID: 32304268    Free PMC article.
Pickering emulsions with ethiodized oil and nanoparticles for slow release of intratumoral anti-CTLA4 immune checkpoint antibodies.
Lambros Tselikas, Thierry de Baere, +9 authors, Aurélien Marabelle.
J Immunother Cancer, 2020 Jun 24; 8(1). PMID: 32571995    Free PMC article.
Advances in targeted therapy for malignant lymphoma.
Li Wang, Wei Qin, +5 authors, Wei-Li Zhao.
Signal Transduct Target Ther, 2020 Apr 17; 5(1). PMID: 32296035    Free PMC article.
Review.
Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression.
Jonathan P O Hebb, Adriane R Mosley, +4 authors, Dean W Felsher.
Cancer Immunol Immunother, 2017 Sep 15; 67(1). PMID: 28905118    Free PMC article.
Combinatorial approach to cancer immunotherapy: strength in numbers.
Anna E Vilgelm, Douglas B Johnson, Ann Richmond.
J Leukoc Biol, 2016 Jun 04; 100(2). PMID: 27256570    Free PMC article.
Review.
A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system.
Aude Burlion, Rodrigo N Ramos, +7 authors, Gilles Marodon.
Oncoimmunology, 2019 May 31; 8(7). PMID: 31143518    Free PMC article.
OX40 and OX40L protein expression of tumor infiltrating lymphocytes in non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers.
Yayi He, Xiaoshen Zhang, +6 authors, Caicun Zhou.
Transl Lung Cancer Res, 2019 Sep 27; 8(4). PMID: 31555511    Free PMC article.
Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis.
Ane Ruiz-de-Angulo, Marc Bilbao-Asensio, +7 authors, Juan C Mareque-Rivas.
iScience, 2020 Sep 13; 23(9). PMID: 32919370    Free PMC article.
The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure.
Tianlin Zhou, Jinrong Peng, +7 authors, Zhiyong Qian.
Bioact Mater, 2020 Oct 03; 6(3). PMID: 33005832    Free PMC article.
T-cell agonists in cancer immunotherapy.
Yeonjoo Choi, Yaoyao Shi, +3 authors, Joud Hajjar.
J Immunother Cancer, 2020 Oct 07; 8(2). PMID: 33020242    Free PMC article.
Review.
Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade.
Weilei Hu, Guosheng Wang, +2 authors, Ming You.
iScience, 2020 Oct 22; 23(10). PMID: 33083746    Free PMC article.
Review.
Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.
Chi Ma, Miaojun Han, +20 authors, Tim F Greten.
Science, 2018 May 26; 360(6391). PMID: 29798856    Free PMC article.
Highly Cited.
An IL-2-grafted antibody immunotherapy with potent efficacy against metastatic cancer.
Dilara Sahin, Natalia Arenas-Ramirez, +5 authors, Onur Boyman.
Nat Commun, 2020 Dec 24; 11(1). PMID: 33353953    Free PMC article.
Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists.
Olivia K Burn, Kef K Prasit, Ian F Hermans.
Cancers (Basel), 2020 Dec 24; 12(12). PMID: 33352882    Free PMC article.
Review.
Harnessing innate immunity in cancer therapy.
Olivier Demaria, Stéphanie Cornen, +3 authors, Eric Vivier.
Nature, 2019 Oct 04; 574(7776). PMID: 31578484
Highly Cited. Review.
Domain binding and isotype dictate the activity of anti-human OX40 antibodies.
Jordana Griffiths, Khiyam Hussain, +18 authors, Mark S Cragg.
J Immunother Cancer, 2021 Jan 12; 8(2). PMID: 33428585    Free PMC article.
Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients.
Izhar S Batth, Long Dao, +11 authors, Shulin Li.
Int J Cancer, 2020 Jun 09; 147(12). PMID: 32506485    Free PMC article.
Peri-tumor administration of controlled release anti-CTLA-4 synergizes with systemic anti-PD-1 to induce systemic antitumor immunity while sparing autoimmune toxicity.
Airi Harui, Sandra M McLachlan, +2 authors, Michael D Roth.
Cancer Immunol Immunother, 2020 Apr 26; 69(9). PMID: 32333082
Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.
Helena Van Damme, Bruno Dombrecht, +26 authors, Jo Agnes Van Ginderachter.
J Immunother Cancer, 2021 Feb 17; 9(2). PMID: 33589525    Free PMC article.
Immunotherapy Goes Local: The Central Role of Lymph Nodes in Driving Tumor Infiltration and Efficacy.
Kim M van Pul, Marieke F Fransen, Rieneke van de Ven, Tanja D de Gruijl.
Front Immunol, 2021 Mar 19; 12. PMID: 33732264    Free PMC article.
Review.
CTLA-4 in Regulatory T Cells for Cancer Immunotherapy.
Navid Sobhani, Dana Rae Tardiel-Cyril, +3 authors, Yong Li.
Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33809974    Free PMC article.
Review.
In vivo NIR-II structured-illumination light-sheet microscopy.
Feifei Wang, Zhuoran Ma, +6 authors, Hongjie Dai.
Proc Natl Acad Sci U S A, 2021 Feb 03; 118(6). PMID: 33526701    Free PMC article.
OX40 as a novel target for the reversal of immune escape in colorectal cancer.
Lin-Hai Yan, Xiao-Liang Liu, +3 authors, Wei-Zhong Tang.
Am J Transl Res, 2021 Apr 13; 13(3). PMID: 33841630    Free PMC article.
Review.
Emerging strategies for treating metastasis.
Mark Esposito, Shridar Ganesan, Yibin Kang.
Nat Cancer, 2021 Apr 27; 2(3). PMID: 33899000    Free PMC article.
Recruitment and Expansion of Tregs Cells in the Tumor Environment-How to Target Them?
Justine Cinier, Margaux Hubert, +5 authors, Christine Ménétrier-Caux.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33924428    Free PMC article.
Review.
Intratumoural administration and tumour tissue targeting of cancer immunotherapies.
Ignacio Melero, Eduardo Castanon, +2 authors, Aurelien Marabelle.
Nat Rev Clin Oncol, 2021 May 20; 18(9). PMID: 34006998    Free PMC article.
Review.
Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection.
Alexa C Glencer, Jasmine M Wong, +7 authors, Michael J Campbell.
NPJ Breast Cancer, 2021 May 27; 7(1). PMID: 34035311    Free PMC article.
Immune Responses against Disseminated Tumor Cells.
Ling Peng, Yongchang Zhang, Zibing Wang.
Cancers (Basel), 2021 Jun 03; 13(11). PMID: 34063848    Free PMC article.
Review.
The Combination Immunotherapy of TLR9 Agonist and OX40 Agonist via Intratumoural Injection for Hepatocellular Carcinoma.
Zhimei Zhou, Liteng Lin, +6 authors, Kangshun Zhu.
J Hepatocell Carcinoma, 2021 Jun 18; 8. PMID: 34136421    Free PMC article.
Non-cationic Material Design for Nucleic Acid Delivery.
Ziwen Jiang, S Thayumanavan.
Adv Ther (Weinh), 2020 Mar 01; 3(3). PMID: 34164572    Free PMC article.
Identification of microenvironment related potential biomarkers of biochemical recurrence at 3 years after prostatectomy in prostate adenocarcinoma.
Xiaoru Sun, Lu Wang, +7 authors, Fuzhong Xue.
Aging (Albany NY), 2021 Jun 17; 13(12). PMID: 34133324    Free PMC article.
Sphingosine-1-phosphate Receptor-1 Agonist Averts the De Novo Generation of Autoreactive T-cells in Murine Acute Graft-versus-Host Disease.
Madeleine Vollmer, Philip Smith, +2 authors, Lukas T Jeker.
Hemasphere, 2021 Jul 16; 5(8). PMID: 34263142    Free PMC article.
Immune Checkpoint Therapy: Tumor Draining Lymph Nodes in the Spotlights.
Marieke F Fransen, Thorbald van Hall, Ferry Ossendorp.
Int J Mol Sci, 2021 Sep 11; 22(17). PMID: 34502307    Free PMC article.
Review.
Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology.
Karen A Autio, Valentina Boni, Rachel W Humphrey, Aung Naing.
Clin Cancer Res, 2019 Oct 12; 26(5). PMID: 31601568    Free PMC article.
Review.
Robust immune response stimulated by in situ injection of CpG/αOX40/cGAMP in αPD-1-resistant malignancy.
Luya Cai, Xuedan Du, +11 authors, Wenfeng Li.
Cancer Immunol Immunother, 2021 Nov 04; 71(7). PMID: 34731284
Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.
Alexander A Pieper, Luke M Zangl, +17 authors, Zachary S Morris.
Front Immunol, 2021 Dec 07; 12. PMID: 34868010    Free PMC article.
Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop.
Francesco Marangoni, Ademi Zhakyp, +10 authors, Thorsten R Mempel.
Cell, 2021 Jun 23; 184(15). PMID: 34157302    Free PMC article.
Development of a fully canine anti-canine CTLA4 monoclonal antibody for comparative translational research in dogs with spontaneous tumors.
Nicola J Mason, Nicholas Chester, +6 authors, Don L Siegel.
MAbs, 2021 Dec 04; 13(1). PMID: 34856888    Free PMC article.
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Improving cancer immunotherapy through nanotechnology.
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Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma.
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