Journal Article
. 2008 Mar; 205(4):825-39.
doi: 10.1084/jem.20071341.

OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection

Silvia Piconese 1 Barbara Valzasina  Mario P Colombo  
Affiliations
  • PMID: 18362171
  •     60 References
  •     171 citations

Abstract

Regulatory T (T reg) cells are the major obstacle to cancer immunotherapy, and their depletion promptly induces conversion of peripheral precursors into T reg cells. We show that T reg cells can be functionally inactivated by OX40 triggering. In tumors, the vast majority of CD4(+) T cells are Foxp3(+) and OX40(bright). However, intratumor injection of the agonist anti-OX40 monoclonal antibody (mAb) OX86, but not anti-CD25 mAb, induces tumor rejection in 80% of mice, an effect that is abrogated by CD8 depletion. Upon intratumor OX40 triggering, increased numbers of infiltrating dendritic cells (DCs) migrate to draining lymph nodes and generate a new wave of tumor-specific cytotoxic T lymphocytes, as detected by tetramer and CD44 staining of node CD8(+) T lymphocytes. Tumor-bearing Rag1-knockout (KO) mice reconstituted with OX40-deficient T reg cells and wild-type (WT) effector T cells, or the reciprocal combination, showed that both T reg and effector T cells must be triggered via OX40 for the tumor to be rejected. Accordingly, WT but not OX40-KO mice receiving intratumor coinjection of OX86 and ovalbumin protein were able to revert tumor-induced tolerization of adoptively transferred OX40-competent OTII T lymphocytes. In conclusion, OX40-mediated inactivation of T reg cell function unleashes nearby DCs, allowing them to induce an adaptive immune response. In addition, the known OX40-dependent delivery of fitness signals to activated T cells is boosted by concurrent T reg cell inhibition. OX40 triggering thus has multiple effects that converge to mediate tumor rejection.

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Helene Pere, Corinne Tanchot, +17 authors, Eric Tartour.
Oncoimmunology, 2012 Jun 28; 1(3). PMID: 22737608    Free PMC article.
Towards curative cancer immunotherapy: overcoming posttherapy tumor escape.
Gang Zhou, Hyam Levitsky.
Clin Dev Immunol, 2012 Jul 11; 2012. PMID: 22778760    Free PMC article.
Review.
OX40 signaling favors the induction of T(H)9 cells and airway inflammation.
Xiang Xiao, Savithri Balasubramanian, +7 authors, Xian Chang Li.
Nat Immunol, 2012 Jul 31; 13(10). PMID: 22842344    Free PMC article.
Highly Cited.
SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into CD4+ FoxP3+ T regulatory cells by production of IFN-γ.
Shravan Madireddi, Rich-Henry Schabowsky, +3 authors, Haval Shirwan.
PLoS One, 2012 Aug 08; 7(8). PMID: 22870329    Free PMC article.
The Role of the PI3K Signaling Pathway in CD4(+) T Cell Differentiation and Function.
Jonathan M Han, Scott J Patterson, Megan K Levings.
Front Immunol, 2012 Aug 21; 3. PMID: 22905034    Free PMC article.
Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype.
Daniel Hirschhorn-Cymerman, Sadna Budhu, +10 authors, Jedd D Wolchok.
J Exp Med, 2012 Sep 26; 209(11). PMID: 23008334    Free PMC article.
Th9 cells promote antitumor immune responses in vivo.
Yong Lu, Sungyoul Hong, +10 authors, Qing Yi.
J Clin Invest, 2012 Oct 16; 122(11). PMID: 23064366    Free PMC article.
Highly Cited.
Advances in targeting cell surface signalling molecules for immune modulation.
Sheng Yao, Yuwen Zhu, Lieping Chen.
Nat Rev Drug Discov, 2013 Feb 02; 12(2). PMID: 23370250    Free PMC article.
Highly Cited. Review.
Influence of tumors on protective anti-tumor immunity and the effects of irradiation.
Gemma A Foulds, Jürgen Radons, +2 authors, Alan G Pockley.
Front Oncol, 2013 Feb 05; 3. PMID: 23378947    Free PMC article.
The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy.
Amy E Moran, Magdalena Kovacsovics-Bankowski, Andrew D Weinberg.
Curr Opin Immunol, 2013 Feb 19; 25(2). PMID: 23414607    Free PMC article.
Review.
Dysregulation of CD4+CD25(high) T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis.
Nalini K Vudattu, Klemen Strle, Allen C Steere, Elise E Drouin.
Arthritis Rheum, 2013 Mar 02; 65(6). PMID: 23450683    Free PMC article.
Agonist antibodies to TNFR molecules that costimulate T and NK cells.
Ignacio Melero, Daniel Hirschhorn-Cymerman, +2 authors, Jedd D Wolchok.
Clin Cancer Res, 2013 Mar 06; 19(5). PMID: 23460535    Free PMC article.
Highly Cited.
Interaction between natural killer cells and regulatory T cells: perspectives for immunotherapy.
Isabela Pedroza-Pacheco, Alejandro Madrigal, Aurore Saudemont.
Cell Mol Immunol, 2013 Mar 26; 10(3). PMID: 23524654    Free PMC article.
Review.
Modulation of tumor immunity by soluble and membrane-bound molecules at the immunological synapse.
Pablo A González, Leandro J Carreño, +3 authors, Alexis M Kalergis.
Clin Dev Immunol, 2013 Mar 28; 2013. PMID: 23533456    Free PMC article.
Review.
Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects.
John Stagg, Bertrand Allard.
Ther Adv Med Oncol, 2013 May 02; 5(3). PMID: 23634195    Free PMC article.
Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.
Derek A Wainwright, Mahua Dey, Alan Chang, Maciej S Lesniak.
Front Immunol, 2013 May 31; 4. PMID: 23720663    Free PMC article.
Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy.
Edwin Bremer.
ISRN Oncol, 2013 Jul 11; 2013. PMID: 23840967    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Immunomodulation via Chemotherapy and Targeted Therapy: A New Paradigm in Breast Cancer Therapy?
John Stagg, Fabrice Andre, Sherene Loi.
Breast Care (Basel), 2013 Aug 02; 7(4). PMID: 23904828    Free PMC article.
Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.
Kui S Voo, Laura Bover, +5 authors, Yong J Liu.
J Immunol, 2013 Sep 10; 191(7). PMID: 24014877    Free PMC article.
Secreted and transmembrane 1A is a novel co-stimulatory ligand.
Duncan Howie, Hugo Garcia Rueda, Marion H Brown, Herman Waldmann.
PLoS One, 2013 Sep 17; 8(9). PMID: 24039998    Free PMC article.
OX40 is a potent immune-stimulating target in late-stage cancer patients.
Brendan D Curti, Magdalena Kovacsovics-Bankowski, +20 authors, Andrew D Weinberg.
Cancer Res, 2013 Nov 02; 73(24). PMID: 24177180    Free PMC article.
Highly Cited.
Update on vaccine development for renal cell cancer.
Nina Chi, Jodi K Maranchie, Leonard J Appleman, Walter J Storkus.
Open Access J Urol, 2010 Jan 01; 2. PMID: 24198621    Free PMC article.
Review.
Intratumoral CD4+ T lymphodepletion sensitizes poorly immunogenic melanomas to immunotherapy with an OX40 agonist.
Susumu Fujiwara, Hiroshi Nagai, +3 authors, Chikako Nishigori.
J Invest Dermatol, 2014 Jan 29; 134(7). PMID: 24468748
Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice.
Judith T Murphy, Andre P Burey, +4 authors, Jedd D Wolchok.
Blood, 2014 Feb 22; 123(14). PMID: 24558202    Free PMC article.
PD-1 blockade and OX40 triggering synergistically protects against tumor growth in a murine model of ovarian cancer.
Zhiqiang Guo, Xin Wang, +3 authors, Shulan Zhang.
PLoS One, 2014 Mar 04; 9(2). PMID: 24586709    Free PMC article.
Highly Cited.
Regulatory T-cell homeostasis: steady-state maintenance and modulation during inflammation.
Kate S Smigiel, Shivani Srivastava, J Michael Stolley, Daniel J Campbell.
Immunol Rev, 2014 Apr 10; 259(1). PMID: 24712458    Free PMC article.
Highly Cited. Review.
Selective targeting of Toll-like receptors and OX40 inhibit regulatory T-cell function in follicular lymphoma.
Kui Shin Voo, Myriam Foglietta, +13 authors, Sattva S Neelapu.
Int J Cancer, 2014 Apr 29; 135(12). PMID: 24771328    Free PMC article.
Combined targeting of costimulatory (OX40) and coinhibitory (CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity.
William L Redmond, Stefanie N Linch, Melissa J Kasiewicz.
Cancer Immunol Res, 2014 Apr 30; 2(2). PMID: 24778278    Free PMC article.
Opening a niche for therapy: local lymphodepletion helps the immune system to fight melanoma.
Karsten Mahnke, Alexander Skorokhod, Stefan Grabbe, Alexander H Enk.
J Invest Dermatol, 2014 Jun 14; 134(7). PMID: 24924759
Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction.
Yun Song, Emilio Margolles-Clark, Allison Bayer, Peter Buchwald.
Br J Pharmacol, 2014 Jun 17; 171(21). PMID: 24930776    Free PMC article.
The "Trojan Horse" approach to tumor immunotherapy: targeting the tumor microenvironment.
Delia Nelson, Scott Fisher, Bruce Robinson.
J Immunol Res, 2014 Jun 24; 2014. PMID: 24955376    Free PMC article.
Review.
p38 MAPK-inhibited dendritic cells induce superior antitumour immune responses and overcome regulatory T-cell-mediated immunosuppression.
Yong Lu, Mingjun Zhang, +9 authors, Qing Yi.
Nat Commun, 2014 Jun 25; 5. PMID: 24957461    Free PMC article.
Cancer immunotherapy in clinical practice -- the past, present, and future.
Gaurav Goel, Weijing Sun.
Chin J Cancer, 2014 Sep 06; 33(9). PMID: 25189717    Free PMC article.
OX40 ligand expressed in glioblastoma modulates adaptive immunity depending on the microenvironment: a clue for successful immunotherapy.
Ichiyo Shibahara, Ryuta Saito, +16 authors, Teiji Tominaga.
Mol Cancer, 2015 Mar 10; 14. PMID: 25744203    Free PMC article.
OX40 Agonists and Combination Immunotherapy: Putting the Pedal to the Metal.
Stefanie N Linch, Michael J McNamara, William L Redmond.
Front Oncol, 2015 Mar 13; 5. PMID: 25763356    Free PMC article.
Highly Cited. Review.
Regulatory T cells turn pathogenic.
Jitao Guo, Xuyu Zhou.
Cell Mol Immunol, 2015 May 06; 12(5). PMID: 25942597    Free PMC article.
Review.
Evolving synergistic combinations of targeted immunotherapies to combat cancer.
Ignacio Melero, David M Berman, +3 authors, John Haanen.
Nat Rev Cancer, 2015 Jul 25; 15(8). PMID: 26205340
Highly Cited. Review.
OX40, OX40L and Autoimmunity: a Comprehensive Review.
Gwilym J Webb, Gideon M Hirschfield, Peter J L Lane.
Clin Rev Allergy Immunol, 2015 Jul 29; 50(3). PMID: 26215166
Review.
Immunosuppressive Mechanisms of Malignant Gliomas: Parallels at Non-CNS Sites.
Powell Perng, Michael Lim.
Front Oncol, 2015 Jul 29; 5. PMID: 26217588    Free PMC article.
Review.
Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies.
Simon Gebremeskel, Brent Johnston.
Oncotarget, 2015 Oct 22; 6(39). PMID: 26486085    Free PMC article.
Review.
Emerging targets in cancer immunotherapy: beyond CTLA-4 and PD-1.
Amer Assal, Justin Kaner, Gopichand Pendurti, Xingxing Zang.
Immunotherapy, 2015 Nov 17; 7(11). PMID: 26567614    Free PMC article.
Review.
Immunostimulation by OX40 Ligand Transgenic Ewing Sarcoma Cells.
Dajana Reuter, Martin S Staege, Caspar D Kühnöl, Jürgen Föll.
Front Oncol, 2015 Nov 19; 5. PMID: 26579494    Free PMC article.
Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination.
Tammy Oth, Joris Vanderlocht, +2 authors, Wilfred T V Germeraad.
Mediators Inflamm, 2016 Mar 17; 2016. PMID: 26980946    Free PMC article.
Review.
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.
Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer.
Ruth J Davis, Carter Van Waes, Clint T Allen.
Oral Oncol, 2016 May 25; 58. PMID: 27215705    Free PMC article.
Review.
Breaking Free of Control: How Conventional T Cells Overcome Regulatory T Cell Suppression.
Emily R Mercadante, Ulrike M Lorenz.
Front Immunol, 2016 Jun 01; 7. PMID: 27242798    Free PMC article.
Review.
The Costimulatory Receptor OX40 Inhibits Interleukin-17 Expression through Activation of Repressive Chromatin Remodeling Pathways.
Xiang Xiao, Xiaomin Shi, +7 authors, Xian Chang Li.
Immunity, 2016 Jun 19; 44(6). PMID: 27317259    Free PMC article.
Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?
Anabelle Visperas, Dario A A Vignali.
J Immunol, 2016 Nov 07; 197(10). PMID: 27815439    Free PMC article.
Review.
Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling.
Prabhakaran Kumar, Khaled Alharshawi, +6 authors, Bellur S Prabhakar.
Sci Rep, 2017 Jan 04; 7. PMID: 28045060    Free PMC article.
New Immunotherapy Strategies in Breast Cancer.
Lin-Yu Yu, Jie Tang, +4 authors, Xiao-Ping Chen.
Int J Environ Res Public Health, 2017 Jan 14; 14(1). PMID: 28085094    Free PMC article.
Review.
TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury.
Peixiang Lan, Yihui Fan, +9 authors, Xian Chang Li.
J Clin Invest, 2017 Apr 25; 127(6). PMID: 28436935    Free PMC article.
T Cells Deficient in the Tyrosine Phosphatase SHP-1 Resist Suppression by Regulatory T Cells.
Emily R Mercadante, Ulrike M Lorenz.
J Immunol, 2017 May 28; 199(1). PMID: 28550200    Free PMC article.
Intratumoral delivery of tumor antigen-loaded DC and tumor-primed CD4+ T cells combined with agonist α-GITR mAb promotes durable CD8+ T-cell-dependent antitumor immunity.
Zuqiang Liu, Xingxing Hao, +5 authors, Zhaoyang You.
Oncoimmunology, 2017 Jul 07; 6(6). PMID: 28680744    Free PMC article.
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.
Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant.
Victor Tkachev, Scott N Furlan, +15 authors, Leslie S Kean.
Sci Transl Med, 2017 Sep 22; 9(408). PMID: 28931653    Free PMC article.
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.
CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy.
Anna Wasiuk, James Testa, +9 authors, Li-Zhen He.
J Immunol, 2017 Nov 08; 199(12). PMID: 29109120    Free PMC article.
Constitutive expression of NF-κB inducing kinase in regulatory T cells impairs suppressive function and promotes instability and pro-inflammatory cytokine production.
Fanny Polesso, Minhazur Sarker, +2 authors, Susan E Murray.
Sci Rep, 2017 Nov 09; 7(1). PMID: 29116141    Free PMC article.
Combination therapy with an OX40L fusion protein and a vaccine targeting the transcription factor twist inhibits metastasis in a murine model of breast cancer.
Anthony S Malamas, Scott A Hammond, Jeffrey Schlom, James W Hodge.
Oncotarget, 2017 Dec 07; 8(53). PMID: 29207606    Free PMC article.
Trial Watch: Immunostimulatory monoclonal antibodies for oncological indications.
Mariona Cabo, Rienk Offringa, +3 authors, Lorenzo Galluzzi.
Oncoimmunology, 2017 Dec 07; 6(12). PMID: 29209572    Free PMC article.
Review.
Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity.
Ronit Mazor, Emily M King, +6 authors, Ira Pastan.
Proc Natl Acad Sci U S A, 2018 Jan 10; 115(4). PMID: 29311317    Free PMC article.
Review.
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.
Harnessing the immune system in the battle against breast cancer.
Elizabeth S Nakasone, Sara A Hurvitz, Kelly E McCann.
Drugs Context, 2018 Feb 20; 7. PMID: 29456568    Free PMC article.
Review.
Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells.
Gap Ryol Lee.
Mediators Inflamm, 2018 Feb 22; 2017. PMID: 29463952    Free PMC article.
Review.
Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein.
Michael D Oberst, Catherine Augé, +19 authors, Scott A Hammond.
Mol Cancer Ther, 2018 Mar 17; 17(5). PMID: 29545330    Free PMC article.
Keeping Tumors in Check: A Mechanistic Review of Clinical Response and Resistance to Immune Checkpoint Blockade in Cancer.
Nicholas Borcherding, Ryan Kolb, +3 authors, Weizhou Zhang.
J Mol Biol, 2018 May 26; 430(14). PMID: 29800567    Free PMC article.
Review.
Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies.
Annelisa M Cornel, Niek P van Til, Jaap Jan Boelens, Stefan Nierkens.
Front Immunol, 2018 Jun 06; 9. PMID: 29867960    Free PMC article.
Review.
Foxp3+ T Regulatory Cells: Still Many Unanswered Questions-A Perspective After 20 Years of Study.
Ethan M Shevach.
Front Immunol, 2018 Jun 06; 9. PMID: 29868011    Free PMC article.
Highly Cited. Review.
The promise and challenges of immune agonist antibody development in cancer.
Patrick A Mayes, Kenneth W Hance, Axel Hoos.
Nat Rev Drug Discov, 2018 Jun 16; 17(7). PMID: 29904196
Highly Cited. Review.
Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.
Ilenia Pacella, Claudio Procaccini, +17 authors, Silvia Piconese.
Proc Natl Acad Sci U S A, 2018 Jun 27; 115(28). PMID: 29941600    Free PMC article.
Highly Cited.
OX40 Costimulation Inhibits Foxp3 Expression and Treg Induction via BATF3-Dependent and Independent Mechanisms.
Xiaolong Zhang, Xiang Xiao, +9 authors, Xian C Li.
Cell Rep, 2018 Jul 19; 24(3). PMID: 30021159    Free PMC article.
Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells.
Jintong Chen, Yinghua Zhao, +8 authors, Siqing Wang.
Front Immunol, 2018 Aug 16; 9. PMID: 30108595    Free PMC article.
New strategies in immunotherapy for lung cancer: beyond PD-1/PD-L1.
Nicolas Villanueva, Lyudmila Bazhenova.
Ther Adv Respir Dis, 2018 Sep 15; 12. PMID: 30215300    Free PMC article.
Review.
OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis.
Patrizia Nanni, Carla De Giovanni, +7 authors, Pier-Luigi Lollini.
Oncoimmunology, 2018 Sep 18; 7(8). PMID: 30221061    Free PMC article.
Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity.
Kathrin Rothfelder, Ilona Hagelstein, +6 authors, Daniela Dörfel.
Neoplasia, 2018 Oct 10; 20(11). PMID: 30300827    Free PMC article.
Regulatory T Cells in Systemic Sclerosis.
Camelia Frantz, Cedric Auffray, Jerome Avouac, Yannick Allanore.
Front Immunol, 2018 Oct 31; 9. PMID: 30374354    Free PMC article.
Review.
High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer.
Erminia Massarelli, Vincent K Lam, +13 authors, John V Heymach.
J Immunother Cancer, 2019 Dec 18; 7(1). PMID: 31843013    Free PMC article.
T-Regulatory Cells In Tumor Progression And Therapy.
Amit Verma, Rohit Mathur, +3 authors, Bilikere S Dwarakanath.
Cancer Manag Res, 2020 Jan 11; 11. PMID: 31920383    Free PMC article.
Review.
Bioprofiling TS/A Murine Mammary Cancer for a Functional Precision Experimental Model.
Carla De Giovanni, Giordano Nicoletti, +3 authors, Patrizia Nanni.
Cancers (Basel), 2019 Dec 01; 11(12). PMID: 31783695    Free PMC article.
Review.
Immune checkpoint modulation enhances HIV-1 antibody induction.
Todd Bradley, Masayuki Kuraoka, +27 authors, Barton F Haynes.
Nat Commun, 2020 Feb 23; 11(1). PMID: 32075963    Free PMC article.
Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.
Yu Fu, Qing Lin, Zhirong Zhang, Ling Zhang.
Acta Pharm Sin B, 2020 Mar 07; 10(3). PMID: 32140389    Free PMC article.
Review.
The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia.
Patrick Williams, Sreyashi Basu, +22 authors, Naval G Daver.
Cancer, 2018 Dec 01; 125(9). PMID: 30500073    Free PMC article.
Highly Cited.
Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies.
Xue Han, Matthew D Vesely.
Int Rev Cell Mol Biol, 2019 Jan 13; 342. PMID: 30635089    Free PMC article.
Review.
Treg cells in autoimmunity: from identification to Treg-based therapies.
Lisa Göschl, Clemens Scheinecker, Michael Bonelli.
Semin Immunopathol, 2019 Apr 07; 41(3). PMID: 30953162
Review.
The promise of CD4+FoxP3+ regulatory T-cell manipulation in vivo: applications for allogeneic hematopoietic stem cell transplantation.
Sabrina Copsel, Dietlinde Wolf, Krishna V Komanduri, Robert B Levy.
Haematologica, 2019 Jun 22; 104(7). PMID: 31221786    Free PMC article.
Review.
In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors.
Danny N Khalil, Nathan Suek, +18 authors, Taha Merghoub.
J Clin Invest, 2019 Jul 23; 129(8). PMID: 31329159    Free PMC article.
Molecular Links between Central Obesity and Breast Cancer.
Alina-Andreea Zimta, Adrian Bogdan Tigu, +3 authors, Ioana Berindan-Neagoe.
Int J Mol Sci, 2019 Oct 31; 20(21). PMID: 31661891    Free PMC article.
Review.
Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy.
Seongju Jeong, Su-Hyung Park.
Immune Netw, 2020 Mar 12; 20(1). PMID: 32158591    Free PMC article.
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.
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.
Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.
Rachel E O'Neill, Xuefang Cao.
Adv Cancer Res, 2019 Jun 17; 143. PMID: 31202358    Free PMC article.
Review.
Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma.
Veronica Mollica, Alessandro Rizzo, +9 authors, Francesco Massari.
Cancers (Basel), 2020 Jun 06; 12(6). PMID: 32498352    Free PMC article.
Review.
Tumor necrosis factor receptor family costimulation increases regulatory T-cell activation and function via NF-κB.
Martina Lubrano di Ricco, Emilie Ronin, +8 authors, Benoît L Salomon.
Eur J Immunol, 2020 Feb 06; 50(7). PMID: 32012260    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.
The clinical promise of immunotherapy in triple-negative breast cancer.
Praveen Vikas, Nicholas Borcherding, Weizhou Zhang.
Cancer Manag Res, 2018 Dec 24; 10. PMID: 30573992    Free PMC article.
Review.
The Therapeutic Strategies of Regulatory T Cells in Malignancies and Stem Cell Transplantations.
Rana G Zaini, Amani A Al-Rehaili.
J Oncol, 2019 Jan 30; 2019. PMID: 30693029    Free PMC article.
Review.
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.
FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells.
Lucia Campos Carrascosa, Adriaan A van Beek, +19 authors, Jaap Kwekkeboom.
J Immunother Cancer, 2020 Sep 10; 8(2). PMID: 32900860    Free PMC article.
OX40-enhanced tumor rejection and effector T cell differentiation decreases with age.
Carl E Ruby, Andrew D Weinberg.
J Immunol, 2009 Jan 22; 182(3). PMID: 19155495    Free PMC article.
Expression of costimulatory TNFR2 induces resistance of CD4+FoxP3- conventional T cells to suppression by CD4+FoxP3+ regulatory T cells.
Xin Chen, Ryoko Hamano, +3 authors, Joost J Oppenheim.
J Immunol, 2010 Jun 08; 185(1). PMID: 20525892    Free PMC article.
CD4+CD25+ Regulatory T Cells Inhibit Natural Killer Cell Hepatocytotoxicity of Hepatitis B Virus Transgenic Mice via Membrane-Bound TGF-β and OX40.
Yongyan Chen, Rui Sun, +3 authors, Zhigang Tian.
J Innate Immun, 2015 Jun 13; 8(1). PMID: 26067079    Free PMC article.
Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer.
Karan Mediratta, Sara El-Sahli, Vanessa D'Costa, Lisheng Wang.
Cancers (Basel), 2020 Dec 02; 12(12). PMID: 33256070    Free PMC article.
Review.
Immune-Checkpoint Inhibitors in B-Cell Lymphoma.
Marc Armengol, Juliana Carvalho Santos, +3 authors, Gaël Roué.
Cancers (Basel), 2021 Jan 13; 13(2). PMID: 33430146    Free PMC article.
Review.
Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression.
Yu Mei, Wenya Linda Bi, +8 authors, Ian F Dunn.
Pituitary, 2021 Jan 26; 24(3). PMID: 33492612
Immune profiling and immunotherapeutic targets in pancreatic cancer.
Felicia L Lenzo, Shumei Kato, +8 authors, Carl Morrison.
Ann Transl Med, 2021 Feb 12; 9(2). PMID: 33569421    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.
Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ.
Renske J E van den Bijgaart, Fabian Schuurmans, +3 authors, Gosse J Adema.
Front Immunol, 2021 May 04; 12. PMID: 33936033    Free PMC article.
Review.
Regulation of mRNA stability by RBPs and noncoding RNAs contributing to the pathogenicity of Th17 cells.
Yiwei Zhang, Zhiyuan Wei, +6 authors, Yi Tian.
RNA Biol, 2020 Dec 12; 18(5). PMID: 33302787    Free PMC article.
Review.
CD40 Activity on Mesenchymal Cells Negatively Regulates OX40L to Maintain Bone Marrow Immune Homeostasis Under Stress Conditions.
Barbara Bassani, Claudio Tripodo, +12 authors, Sabina Sangaletti.
Front Immunol, 2021 Jun 05; 12. PMID: 34084166    Free PMC article.
OX40 agonist combined with irreversible electroporation synergistically eradicates established tumors and drives systemic antitumor immune response in a syngeneic pancreatic cancer model.
Qi-Wei Zhang, Xiao-Xia Guo, +4 authors, Xiao-Yi Ding.
Am J Cancer Res, 2021 Jul 13; 11(6). PMID: 34249428    Free PMC article.
Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.
Daniele E Mascarelli, Rhubia S M Rosa, +5 authors, Marcio C Bajgelman.
Front Cell Dev Biol, 2021 Jul 20; 9. PMID: 34277638    Free PMC article.
Review.
Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.
Hiroyoshi Nishikawa, Shohei Koyama.
J Immunother Cancer, 2021 Aug 01; 9(7). PMID: 34330764    Free PMC article.
Review.
Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells.
Sijia Zhang, Lingjun Zhan, +3 authors, Haiping Zhao.
Int J Biol Sci, 2021 Sep 14; 17(13). PMID: 34512154    Free PMC article.
Review.
OX40-targeted immune agonist antibodies induce potent antitumor immune responses without inducing liver damage in mice.
Yee C Tee, Stephen J Blake, David J Lynn.
FASEB Bioadv, 2021 Oct 12; 3(10). PMID: 34632317    Free PMC article.
Spatial Mapping and Immunomodulatory Role of the OX40/OX40L Pathway in Human Non-Small Cell Lung Cancer.
Angelo Porciuncula, Micaela Morgado, +5 authors, Kurt A Schalper.
Clin Cancer Res, 2021 Sep 15; 27(22). PMID: 34518312    Free PMC article.
Tnfrsf4-expressing regulatory T cells promote immune escape of chronic myeloid leukemia stem cells.
Magdalena Hinterbrandner, Viviana Rubino, +6 authors, Carsten Riether.
JCI Insight, 2021 Nov 03; 6(23). PMID: 34727093    Free PMC article.
Approaches of the Innate Immune System to Ameliorate Adaptive Immunotherapy for B-Cell Non-Hodgkin Lymphoma in Their Microenvironment.
Takashi Watanabe.
Cancers (Basel), 2022 Jan 12; 14(1). PMID: 35008305    Free PMC article.
Review.
The Pyroptosis-Related Gene Signature Predicts the Prognosis of Hepatocellular Carcinoma.
Shuqiao Zhang, Xinyu Li, +3 authors, Weihong Kuang.
Front Mol Biosci, 2022 Jan 21; 8. PMID: 35047554    Free PMC article.
Boosting antitumor response with PSMA-targeted immunomodulatory VLPs, harboring costimulatory TNFSF ligands and GM-CSF cytokine.
Soledad Palameta, Andrea J Manrique-Rincón, +6 authors, Marcio C Bajgelman.
Mol Ther Oncolytics, 2022 Mar 15; 24. PMID: 35284623    Free PMC article.
Addressing the Elephant in the Immunotherapy Room: Effector T-Cell Priming versus Depletion of Regulatory T-Cells by Anti-CTLA-4 Therapy.
Megan M Y Hong, Saman Maleki Vareki.
Cancers (Basel), 2022 Mar 26; 14(6). PMID: 35326731    Free PMC article.
Review.
Prevalence of intratumoral regulatory T cells expressing neuropilin-1 is associated with poorer outcomes in patients with cancer.
Christopher A Chuckran, Anthony R Cillo, +26 authors, Dario A A Vignali.
Sci Transl Med, 2021 Dec 09; 13(623). PMID: 34878821    Free PMC article.