Journal Article
. 2013 Nov; 210(13):2803-11.
doi: 10.1084/jem.20130678.

Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection

Johannes Vom Berg 1 Melissa Vrohlings  Sergio Haller  Aladin Haimovici  Paulina Kulig  Anna Sledzinska  Michael Weller  Burkhard Becher  
Affiliations
  • PMID: 24277150
  •     32 References
  •     87 citations

Abstract

Glioblastomas (GBs) are the most aggressive form of primary brain cancer and virtually incurable. Accumulation of regulatory T (T reg) cells in GBs is thought to contribute to the dampening of antitumor immunity. Using a syngeneic mouse model for GB, we tested whether local delivery of cytokines could render the immunosuppressive GB microenvironment conducive to an antitumor immune response. IL-12 but not IL-23 reversed GB-induced immunosuppression and led to tumor clearance. In contrast to models of skin or lung cancer, IL-12-mediated glioma rejection was T cell dependent and elicited potent immunological memory. To translate these findings into a clinically relevant setting, we allowed for GB progression before initiating therapy. Combined intratumoral IL-12 application with systemic blockade of the co-inhibitory receptor CTLA-4 on T cells led to tumor eradication even at advanced disease stages where monotherapy with either IL-12 or CTLA-4 blockade failed. The combination of IL-12 and CTLA-4 blockade acts predominantly on CD4(+) cells, causing a drastic decrease in FoxP3(+) T reg cells and an increase in effector T (T eff) cells. Our data provide compelling preclinical findings warranting swift translation into clinical trials in GB and represent a promising approach to increase response rates of CTLA-4 blockade in solid tumors.

Intracerebral interleukin 12 induces glioma rejection in the brain predominantly by CD8+ T cells and independently of interferon-gamma.
Marcus Vetter, Markus J Hofer, +2 authors, Axel Pagenstecher.
J Neuropathol Exp Neurol, 2009 Jun 16; 68(5). PMID: 19525900
Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.
J Cui, T Shin, +7 authors, M Taniguchi.
Science, 1997 Dec 31; 278(5343). PMID: 9374462
Highly Cited.
Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors.
Pankaj Agarwalla, Zachary Barnard, +2 authors, William T Curry.
J Immunother, 2012 May 12; 35(5). PMID: 22576343    Free PMC article.
In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma.
Yunhui Liu, Moneeb Ehtesham, +5 authors, John S Yu.
Cancer Gene Ther, 2002 Mar 28; 9(1). PMID: 11916248
Prognostic significance and mechanism of Treg infiltration in human brain tumors.
Joannes F M Jacobs, Albert J Idema, +4 authors, Gosse J Adema.
J Neuroimmunol, 2010 Jun 12; 225(1-2). PMID: 20537408
Perforin-dependent NK cell cytotoxicity is sufficient for anti-metastatic effect of IL-12.
T Kodama, K Takeda, +6 authors, K Okumura.
Eur J Immunol, 1999 May 06; 29(4). PMID: 10229107
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline.
Johannes Vom Berg, Stefan Prokop, +10 authors, Frank L Heppner.
Nat Med, 2012 Nov 28; 18(12). PMID: 23178247
Highly Cited.
Standards of care for treatment of recurrent glioblastoma--are we there yet?
Michael Weller, Timothy Cloughesy, James R Perry, Wolfgang Wick.
Neuro Oncol, 2012 Nov 09; 15(1). PMID: 23136223    Free PMC article.
Highly Cited. Review.
Interleukin-23-expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma.
Xiangpeng Yuan, Jinwei Hu, +2 authors, John S Yu.
Cancer Res, 2006 Mar 03; 66(5). PMID: 16510582
IL-15 regulates homeostasis and terminal maturation of NKT cells.
Laura E Gordy, Jelena S Bezbradica, +9 authors, Sebastian Joyce.
J Immunol, 2011 Nov 16; 187(12). PMID: 22084435    Free PMC article.
A balance of interleukin-12 and -23 in cancer.
Shin Foong Ngiow, Michele W L Teng, Mark J Smyth.
Trends Immunol, 2013 Aug 21; 34(11). PMID: 23954142
Review.
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
Lucy S K Walker, David M Sansom.
Nat Rev Immunol, 2011 Nov 26; 11(12). PMID: 22116087
Highly Cited.
IL-23 promotes tumour incidence and growth.
John L Langowski, Xueqing Zhang, +7 authors, Martin Oft.
Nature, 2006 May 12; 442(7101). PMID: 16688182
Highly Cited.
IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46.
Maya Eisenring, Johannes vom Berg, +2 authors, Burkhard Becher.
Nat Immunol, 2010 Oct 12; 11(11). PMID: 20935648
Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production.
J P Leonard, M L Sherman, +7 authors, J L Ryan.
Blood, 1997 Nov 05; 90(7). PMID: 9326219
Highly Cited.
Mouse models for melanoma: a personal perspective.
Jürgen C Becker, Roland Houben, +3 authors, Ralph A Reisfeld.
Exp Dermatol, 2009 Oct 24; 19(2). PMID: 19849715
Review.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo.
Martin Uhl, Steffen Aulwurm, +12 authors, Michael Weller.
Cancer Res, 2004 Nov 03; 64(21). PMID: 15520202
Highly Cited.
Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12.
T Joki, T Kikuchi, +3 authors, T Ohno.
Int J Cancer, 1999 Jul 27; 82(5). PMID: 10417770
Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12.
Ryuya Yamanaka, Susan A Zullo, +5 authors, Kleanthis G Xanthopoulos.
J Neurosurg, 2002 Sep 26; 97(3). PMID: 12296646
CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo.
Oliver M Grauer, Stefan Nierkens, +5 authors, Gosse J Adema.
Int J Cancer, 2007 Feb 23; 121(1). PMID: 17315190
Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies.
M B Atkins, M J Robertson, +12 authors, M L Sherman.
Clin Cancer Res, 1997 Mar 01; 3(3). PMID: 9815699
Highly Cited.
Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function.
Peter E Fecci, Hidenobu Ochiai, +7 authors, John H Sampson.
Clin Cancer Res, 2007 Apr 04; 13(7). PMID: 17404100
Highly Cited.
Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells.
Jinwei Hu, Xiangpeng Yuan, +5 authors, John S Yu.
Cancer Res, 2006 Sep 05; 66(17). PMID: 16951206
Glioma immunotherapy by IL-21 gene-modified cells or by recombinant IL-21 involves antibody responses.
Antonio Daga, Anna Maria Orengo, +5 authors, Giorgio Corte.
Int J Cancer, 2007 Jun 22; 121(8). PMID: 17582604
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.
Induction of an antitumor immunological response by an intratumoral injection of dendritic cells pulsed with genetically engineered Semliki Forest virus to produce interleukin-18 combined with the systemic administration of interleukin-12.
Ryuya Yamanaka, Naoto Tsuchiya, +6 authors, Kleanthis G Xanthopoulos.
J Neurosurg, 2003 Oct 22; 99(4). PMID: 14567611
Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy.
Tünde Szatmári, Katalin Lumniczky, +4 authors, Géza Sáfrány.
Cancer Sci, 2006 Jun 01; 97(6). PMID: 16734735
Antitumor and antimetastatic activity of IL-23.
Chia-Hui Lo, Shan-Chih Lee, +8 authors, Mi-Hua Tao.
J Immunol, 2003 Jul 09; 171(2). PMID: 12847224
CTLA-4 blockade in tumor models: an overview of preclinical and translational research.
Joseph F Grosso, Maria N Jure-Kunkel.
Cancer Immun, 2013 Feb 08; 13. PMID: 23390376    Free PMC article.
Highly Cited. Review.
Interleukin-12 in anti-tumor immunity and immunotherapy.
Mario P Colombo, Giorgio Trinchieri.
Cytokine Growth Factor Rev, 2002 Mar 20; 13(2). PMID: 11900991
Highly Cited. Review.
Microenvironmental clues for glioma immunotherapy.
Michael Platten, Katharina Ochs, +2 authors, Wolfgang Wick.
Curr Neurol Neurosci Rep, 2014 Mar 08; 14(4). PMID: 24604058
Review.
Antibody-based immunotherapy for malignant glioma.
Patrick C Gedeon, Katherine A Riccione, Peter E Fecci, John H Sampson.
Semin Oncol, 2014 Sep 01; 41(4). PMID: 25173142    Free PMC article.
Review.
New insights into IL-12-mediated tumor suppression.
S Tugues, S H Burkhard, +5 authors, B Becher.
Cell Death Differ, 2014 Sep 06; 22(2). PMID: 25190142    Free PMC article.
Highly Cited. Review.
Immunotherapy advances for glioblastoma.
David A Reardon, Gordon Freeman, +7 authors, Glenn Dranoff.
Neuro Oncol, 2014 Sep 06; 16(11). PMID: 25190673    Free PMC article.
Highly Cited. Review.
Targeting the tumor microenvironment to enhance antitumor immune responses.
Kevin Van der Jeught, Lukasz Bialkowski, +7 authors, Karine Breckpot.
Oncotarget, 2015 Feb 16; 6(3). PMID: 25682197    Free PMC article.
Review.
Biomarkers for glioma immunotherapy: the next generation.
Jennifer S Sims, Timothy H Ung, +2 authors, Jeffrey N Bruce.
J Neurooncol, 2015 Mar 01; 123(3). PMID: 25724916    Free PMC article.
Review.
Sui generis: gene therapy and delivery systems for the treatment of glioblastoma.
J Robert Kane, Jason Miska, +3 authors, Maciej S Lesniak.
Neuro Oncol, 2015 Mar 10; 17 Suppl 2. PMID: 25746089    Free PMC article.
Review.
Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma.
Serena Pellegatta, Lorella Valletta, +8 authors, Gaetano Finocchiaro.
Acta Neuropathol Commun, 2015 Apr 08; 3. PMID: 25849072    Free PMC article.
A mass spectrometric-derived cell surface protein atlas.
Damaris Bausch-Fluck, Andreas Hofmann, +17 authors, Bernd Wollscheid.
PLoS One, 2015 Apr 22; 10(3). PMID: 25894527    Free PMC article.
Highly Cited.
FGL2 as a Multimodality Regulator of Tumor-Mediated Immune Suppression and Therapeutic Target in Gliomas.
Jun Yan, Ling-Yuan Kong, +5 authors, Shulin Li.
J Natl Cancer Inst, 2015 May 15; 107(8). PMID: 25971300    Free PMC article.
TGF-β signaling and its targeting for glioma treatment.
Jianfeng Han, Christopher A Alvarez-Breckenridge, Qi-En Wang, Jianhua Yu.
Am J Cancer Res, 2015 Jun 06; 5(3). PMID: 26045979    Free PMC article.
Highly Cited. Review.
Concepts of immunotherapy for glioma.
Mira A Patel, Drew M Pardoll.
J Neurooncol, 2015 Jun 14; 123(3). PMID: 26070552    Free PMC article.
Review.
Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study.
David J Klinke.
J Immunother Cancer, 2015 Jun 18; 3. PMID: 26082838    Free PMC article.
Review.
IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases.
Michele W L Teng, Edward P Bowman, +4 authors, Daniel J Cua.
Nat Med, 2015 Jun 30; 21(7). PMID: 26121196
Highly Cited. Review.
Inflammation-associated genes: risks and benefits to Foxp3+ regulatory T-cell function.
Richard A O'Connor, Stephen M Anderton.
Immunology, 2015 Jul 21; 146(2). PMID: 26190495    Free PMC article.
Review.
Making many from few: IL-12p40 as a model for the combinatorial assembly of heterodimeric cytokines.
Kaveh Abdi, Nevil J Singh.
Cytokine, 2015 Aug 06; 76(1). PMID: 26242928    Free PMC article.
Review.
Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator.
M-C Chang, Y-L Chen, +5 authors, W-F Cheng.
Gene Ther, 2015 Aug 12; 23(1). PMID: 26262583
An Update on the Role of Immunotherapy and Vaccine Strategies for Primary Brain Tumors.
Martha R Neagu, David A Reardon.
Curr Treat Options Oncol, 2015 Oct 12; 16(11). PMID: 26454859
Review.
Immunosuppressive mechanisms in glioblastoma.
Edjah K Nduom, Michael Weller, Amy B Heimberger.
Neuro Oncol, 2015 Oct 31; 17 Suppl 7. PMID: 26516226    Free PMC article.
Highly Cited. Review.
Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy.
Anna Śledzińska, Laurie Menger, +2 authors, Sergio A Quezada.
Mol Oncol, 2015 Nov 19; 9(10). PMID: 26578451    Free PMC article.
Review.
Overview of current immunotherapeutic strategies for glioma.
Anda-Alexandra Calinescu, Neha Kamran, +3 authors, Maria Graciela Castro.
Immunotherapy, 2015 Nov 26; 7(10). PMID: 26598957    Free PMC article.
Review.
In situ vaccination: Cancer immunotherapy both personalized and off-the-shelf.
Linda Hammerich, Adam Binder, Joshua D Brody.
Mol Oncol, 2015 Dec 04; 9(10). PMID: 26632446    Free PMC article.
Review.
Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells.
Xiaojing Ma, Wenjun Yan, +5 authors, Fang Wei.
F1000Res, 2016 Feb 27; 4. PMID: 26918147    Free PMC article.
Highly Cited. Review.
Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers.
Takuro Saito, Hiroyoshi Nishikawa, +19 authors, Shimon Sakaguchi.
Nat Med, 2016 Apr 26; 22(6). PMID: 27111280
Highly Cited.
Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet.
Danielle M Lussier, Eric C Woolf, +3 authors, Adrienne C Scheck.
BMC Cancer, 2016 May 15; 16. PMID: 27178315    Free PMC article.
Recent advances and future of immunotherapy for glioblastoma.
Neha Kamran, Alexandra Calinescu, +7 authors, Maria G Castro.
Expert Opin Biol Ther, 2016 Jul 14; 16(10). PMID: 27411023    Free PMC article.
Review.
Prioritization schema for immunotherapy clinical trials in glioblastoma.
Tiffany R Hodges, Sherise D Ferguson, +17 authors, Amy B Heimberger.
Oncoimmunology, 2016 Jul 30; 5(6). PMID: 27471611    Free PMC article.
Review.
Harnessing immunosurveillance: current developments and future directions in cancer immunotherapy.
Maureen L Drakes, Patrick J Stiff.
Immunotargets Ther, 2014 Jan 01; 3. PMID: 27471706    Free PMC article.
Review.
High-grade glioma management and response assessment-recent advances and current challenges.
M N Khan, A M Sharma, +4 authors, M Essig.
Curr Oncol, 2016 Aug 19; 23(4). PMID: 27536188    Free PMC article.
Review.
Anti-GITR therapy promotes immunity against malignant glioma in a murine model.
Jason Miska, Aida Rashidi, +4 authors, Maciej S Lesniak.
Cancer Immunol Immunother, 2016 Oct 14; 65(12). PMID: 27734112    Free PMC article.
Targeting immune checkpoints in malignant glioma.
Xuhao Zhang, Shan Zhu, +3 authors, Jingtao Chen.
Oncotarget, 2016 Oct 21; 8(4). PMID: 27756892    Free PMC article.
Review.
IL-12 protects from psoriasiform skin inflammation.
Paulina Kulig, Stephanie Musiol, +11 authors, Burkhard Becher.
Nat Commun, 2016 Nov 29; 7. PMID: 27892456    Free PMC article.
Interleukin-12 bypasses common gamma-chain signalling in emergency natural killer cell lymphopoiesis.
Isabel Ohs, Maries van den Broek, +5 authors, Burkhard Becher.
Nat Commun, 2016 Dec 17; 7. PMID: 27982126    Free PMC article.
Immunological mechanisms of intravesical chitosan/interleukin-12 immunotherapy against murine bladder cancer.
Sean G Smith, John L Baltz, +3 authors, David A Zaharoff.
Oncoimmunology, 2017 Feb 16; 6(1). PMID: 28197381    Free PMC article.
The Role of Immune Checkpoint Inhibition in the Treatment of Brain Tumors.
Andrew S Luksik, Russell Maxwell, Tomas Garzon-Muvdi, Michael Lim.
Neurotherapeutics, 2017 Mar 05; 14(4). PMID: 28258545    Free PMC article.
Review.
Immune Checkpoint Inhibitors in Gliomas.
Aaron C Tan, Amy B Heimberger, Mustafa Khasraw.
Curr Oncol Rep, 2017 Mar 18; 19(4). PMID: 28303490
Review.
Dendritic cell based vaccination strategy: an evolving paradigm.
Anna C Filley, Mahua Dey.
J Neurooncol, 2017 Apr 24; 133(2). PMID: 28434112    Free PMC article.
Review.
Therapeutic benefit of Salmonella attributed to LPS and TNF-α is exhaustible and dictated by tumor susceptibility.
Dino Kocijancic, Sara Leschner, +4 authors, Siegfried Weiss.
Oncotarget, 2017 Apr 27; 8(22). PMID: 28445131    Free PMC article.
Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis.
Zenan Zhang, Wenjiao Zheng, +4 authors, Shaoheng He.
J Transl Med, 2017 May 04; 15(1). PMID: 28460633    Free PMC article.
Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate corresponding biomarkers-based clinical predictions in glioblastoma.
Abhishek D Garg, Lien Vandenberk, +5 authors, Patrizia Agostinis.
Oncoimmunology, 2017 May 17; 6(4). PMID: 28507806    Free PMC article.
History and current state of immunotherapy in glioma and brain metastasis.
Tresa McGranahan, Gordon Li, Seema Nagpal.
Ther Adv Med Oncol, 2017 May 23; 9(5). PMID: 28529551    Free PMC article.
Review.
Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs.
Kathrin Nussbaum, Sara H Burkhard, +6 authors, Burkhard Becher.
J Exp Med, 2017 Jul 13; 214(8). PMID: 28698286    Free PMC article.
Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade.
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin.
Cancer Cell, 2017 Aug 16; 32(2). PMID: 28810147    Free PMC article.
Highly Cited.
Enhanced Expression of IL-18 and IL-18BP in Plasma of Patients with Eczema: Altered Expression of IL-18BP and IL-18 Receptor on Mast Cells.
Yalin Hu, Junling Wang, +5 authors, Shaoheng He.
Mediators Inflamm, 2017 Aug 26; 2017. PMID: 28839348    Free PMC article.
Role of IL-18 in atopic asthma is determined by balance of IL-18/IL-18BP/IL-18R.
Huiyun Zhang, Junling Wang, +3 authors, Shaoheng He.
J Cell Mol Med, 2017 Sep 19; 22(1). PMID: 28922563    Free PMC article.
An immunocompetent mouse model of human glioblastoma.
Samantha Semenkow, Shen Li, +9 authors, Piotr Walczak.
Oncotarget, 2017 Oct 06; 8(37). PMID: 28977847    Free PMC article.
Neutrophils in Gliomas.
Matteo Massara, Pasquale Persico, +4 authors, Raffaella Bonecchi.
Front Immunol, 2017 Nov 11; 8. PMID: 29123517    Free PMC article.
Review.
Age-associated and therapy-induced alterations in the cellular microenvironment of experimental gliomas.
Hannah Schneider, Birthe Lohmann, +6 authors, Michael Weller.
Oncotarget, 2017 Nov 21; 8(50). PMID: 29152068    Free PMC article.
Blocking CTLA-4 while priming with a whole cell vaccine reshapes the oligoclonal T cell infiltrate and eradicates tumors in an orthotopic glioma model.
Cameron S Field, Martin K Hunn, +3 authors, Ian F Hermans.
Oncoimmunology, 2018 Jan 04; 7(1). PMID: 29296535    Free PMC article.
Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas.
Anna Filley, Mario Henriquez, +7 authors, Mahua Dey.
J Neurooncol, 2018 Jan 14; 137(3). PMID: 29330750    Free PMC article.
Current state and future prospects of immunotherapy for glioma.
Neha Kamran, Mahmoud S Alghamri, +6 authors, Maria G Castro.
Immunotherapy, 2018 Feb 10; 10(4). PMID: 29421984    Free PMC article.
Review.
Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma.
John A Barrett, Hongliang Cai, +7 authors, Francois Lebel.
Cancer Gene Ther, 2018 May 15; 25(5-6). PMID: 29755109    Free PMC article.
Adjuvant Therapy Using Mistletoe Containing Drugs Boosts the T-Cell-Mediated Killing of Glioma Cells and Prolongs the Survival of Glioma Bearing Mice.
Sonja Schötterl, Stephan M Huber, +2 authors, Ulrike Naumann.
Evid Based Complement Alternat Med, 2018 Sep 19; 2018. PMID: 30224928    Free PMC article.
Receptor-Targeted Glial Brain Tumor Therapies.
Puja Sharma, Waldemar Debinski.
Int J Mol Sci, 2018 Oct 28; 19(11). PMID: 30366424    Free PMC article.
Review.
Glioblastoma Treatment Modalities besides Surgery.
Hao Zhang, Ruizhe Wang, +3 authors, Fan Fan.
J Cancer, 2019 Oct 11; 10(20). PMID: 31598150    Free PMC article.
Review.
Biological intratumoral therapy for the high-grade glioma part II: vector- and cell-based therapies and radioimmunotherapy.
Joshua Loya, Charlie Zhang, +2 authors, Santosh Kesari.
CNS Oncol, 2019 Nov 22; 8(3). PMID: 31747784    Free PMC article.
Review.
Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming.
Krzysztof Krawczyk, Leo Scheller, Hyojin Kim, Martin Fussenegger.
Nat Commun, 2020 Feb 01; 11(1). PMID: 32001704    Free PMC article.
Biochemical re-programming of human dermal stem cells to neurons by increasing mitochondrial membrane potential.
He Liu, Zhaoyue He, +6 authors, Hans-Uwe Simon.
Cell Death Differ, 2018 Aug 30; 26(6). PMID: 30154448    Free PMC article.
T lymphocyte-targeted immune checkpoint modulation in glioma.
William James Kelly, Amber Jin Giles, Mark Gilbert.
J Immunother Cancer, 2020 Feb 14; 8(1). PMID: 32051289    Free PMC article.
Review.
Brain Tumor Microenvironment and Host State: Implications for Immunotherapy.
William Tomaszewski, Luis Sanchez-Perez, Thomas F Gajewski, John H Sampson.
Clin Cancer Res, 2019 Feb 26; 25(14). PMID: 30804019    Free PMC article.
Highly Cited. Review.
Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors.
Andy S Ding, Denis Routkevitch, Christina Jackson, Michael Lim.
Front Immunol, 2019 Aug 10; 10. PMID: 31396227    Free PMC article.
Review.
Induction of anti-cancer T cell immunity by in situ vaccination using systemically administered nanomedicines.
Geoffrey M Lynn, Richard Laga, Christopher M Jewell.
Cancer Lett, 2019 Jun 12; 459. PMID: 31185250    Free PMC article.
Review.
Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling.
Shengrong Long, Mingdong Li, +2 authors, Guangyu Li.
Aging (Albany NY), 2020 Apr 21; 12(8). PMID: 32310827    Free PMC article.
Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial.
E Antonio Chiocca, John S Yu, +19 authors, Laurence J N Cooper.
Sci Transl Med, 2019 Aug 16; 11(505). PMID: 31413142    Free PMC article.
Highly Cited.
Interleukin (IL)-12 and IL-23 and Their Conflicting Roles in Cancer.
Juming Yan, Mark J Smyth, Michele W L Teng.
Cold Spring Harb Perspect Biol, 2017 Jul 19; 10(7). PMID: 28716888    Free PMC article.
Review.
Immune checkpoint inhibitors: Advances and impact in neuro-oncology.
Jawad Fares, Mohamad Y Fares, Youssef Fares.
Surg Neurol Int, 2019 Feb 21; 10. PMID: 30783540    Free PMC article.
Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy.
Amber Kerstetter-Fogle, Sourabh Shukla, +4 authors, Nicole F Steinmetz.
Cancers (Basel), 2019 Apr 13; 11(4). PMID: 30974896    Free PMC article.
Localized Interleukin-12 for Cancer Immunotherapy.
Khue G Nguyen, Maura R Vrabel, +4 authors, David A Zaharoff.
Front Immunol, 2020 Nov 13; 11. PMID: 33178203    Free PMC article.
Review.
Induction of Durable Antitumor Response by a Novel Oncolytic Herpesvirus Expressing Multiple Immunomodulatory Transgenes.
Dmitry V Chouljenko, Jun Ding, +9 authors, William Wei-Guo Jia.
Biomedicines, 2020 Nov 14; 8(11). PMID: 33182232    Free PMC article.
Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.
Davide Mangani, Michael Weller, +6 authors, Hannah Schneider.
Neuro Oncol, 2016 Jun 12; 18(12). PMID: 27286797    Free PMC article.
PD-L1 checkpoint blockade delivered by retroviral replicating vector confers anti-tumor efficacy in murine tumor models.
Leah A Mitchell, Kader Yagiz, +14 authors, Amy H Lin.
Oncotarget, 2019 May 02; 10(23). PMID: 31040917    Free PMC article.
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma.
Giulia Agliardi, Anna Rita Liuzzi, +17 authors, Burkhard Becher.
Nat Commun, 2021 Jan 21; 12(1). PMID: 33469002    Free PMC article.
Oral administration of Bifidobacterium breve promotes antitumor efficacy via dendritic cells-derived interleukin 12.
Qingxiang Li, Yuke Li, +5 authors, Chuanbin Guo.
Oncoimmunology, 2021 Feb 05; 10(1). PMID: 33537172    Free PMC article.
Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development.
Tomasz M Grzywa, Magdalena Justyniarska, Dominika Nowis, Jakub Golab.
Cancers (Basel), 2021 Mar 07; 13(4). PMID: 33669537    Free PMC article.
Review.
Pathogenetic Features and Current Management of Glioblastoma.
Hong-My Nguyen, Kirsten Guz-Montgomery, Devin B Lowe, Dipongkor Saha.
Cancers (Basel), 2021 Mar 07; 13(4). PMID: 33670551    Free PMC article.
Review.
A Novel Immune-Related Prognostic Biomarker and Target Associated With Malignant Progression of Glioma.
Yu Zhang, Xin Yang, +5 authors, Hu-Bin Duan.
Front Oncol, 2021 May 04; 11. PMID: 33937046    Free PMC article.
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.
N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors.
Lei Zhan, Junhui Zhang, +7 authors, Yunxia Cao.
Front Cell Dev Biol, 2021 Oct 08; 9. PMID: 34616742    Free PMC article.
Review.
IL-7 coupled with IL-12 increases intratumoral T cell clonality, leading to complete regression of non-immunogenic tumors.
Mamoru Tasaki, Midori Yamashita, +2 authors, Shinsuke Nakao.
Cancer Immunol Immunother, 2021 Apr 29; 70(12). PMID: 33909103    Free PMC article.
Intratumoral expression of IL-12 from lentiviral or RNA vectors acts synergistically with TLR4 agonist (GLA) to generate anti-tumor immunological memory.
Jardin A Leleux, Tina C Albershardt, +5 authors, Peter Berglund.
PLoS One, 2021 Dec 03; 16(12). PMID: 34855754    Free PMC article.
Glioma targeted therapy: insight into future of molecular approaches.
Keyang Yang, Zhijing Wu, +11 authors, Quan Cheng.
Mol Cancer, 2022 Feb 10; 21(1). PMID: 35135556    Free PMC article.
Review.
Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization.
Zhuang Li, Wen-Juan Fu, +14 authors, Xiao-Hong Yao.
J Exp Clin Cancer Res, 2022 Feb 24; 41(1). PMID: 35193644    Free PMC article.
HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies.
Fabio Morandi, Irma Airoldi.
Int J Mol Sci, 2022 Mar 26; 23(6). PMID: 35328349    Free PMC article.
Review.
The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?
Lucas Henrique Rodrigues da Silva, Luana Correia Croda Catharino, +2 authors, José Alexandre Marzagão Barbuto.
Biomedicines, 2022 Feb 26; 10(2). PMID: 35203609    Free PMC article.
Review.
Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.
Aria Sabbagh, Kevin Beccaria, +18 authors, Amy B Heimberger.
Clin Cancer Res, 2021 May 26; 27(15). PMID: 34031054    Free PMC article.
Emerging therapies for glioblastoma: current state and future directions.
Liang Rong, Ni Li, Zhenzhen Zhang.
J Exp Clin Cancer Res, 2022 Apr 17; 41(1). PMID: 35428347    Free PMC article.
Review.
Identification of an endoplasmic reticulum stress-related signature associated with clinical prognosis and immune therapy in glioma.
Lianxin Li, Zhihao Yang, +4 authors, Bing Zhao.
BMC Neurol, 2022 May 26; 22(1). PMID: 35614390