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Optimization of Immune Checkpoint Blockade via a Multiscale Model System [PDF]

Computational and Systems Oncology
Cancer progresses when cancer cells selectively bind to inhibitory receptors on a T cell surface, downregulating tumor immune response. One standard‐of‐care strategy to combat this process is immune checkpoint blockade.
Anne M. Talkington, Anthony J. Kearsley
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MCT4 blockade increases the efficacy of immune checkpoint blockade

Journal for ImmunoTherapy of Cancer, 2023
Background & Aims Intratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for ...
Christian Schmidl, Wolfgang Herr, Nathalie Babl, Sonja-Maria Decking, Florian Voll, Michael Althammer, Ada Sala-Hojman, Roberta Ferretti, Clarissa Korf, Lisa Schmidleithner, Benedikt Nerb, Carina Matos, Gudrun E Koehl, Peter Siska, Christina Bruss, Fabian Kellermeier, Katja Dettmer, Peter J Oefner, Marvin Wichland, Ines Ugele, Christopher Bohr, Shivapriya Ramaswamy, Timo Heinrich, Christian Herhaus, Marina Kreutz, Kathrin Renner   +25 more
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Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model

Haematologica, 2021
We have developed a personalized vaccine whereby patient derived leukemia cells are fused to autologous dendritic cells, evoking a polyclonal T cell response against shared and neo-antigens.
Dina Stroopinsky, Jessica Liegel, Manoj Bhasin, Giulia Cheloni, Beena Thomas, Swati Bhasin, Ruchit Panchal, Haider Ghiasuddin, Maryam Rahimian, Myrna Nahas, Shira Orr, Marzia Capelletti, Daniela Torres, Cansu Tacettin, Matthew Weinstock, Lina Bisharat, Adam Morin, Kathleen M. Mahoney, Benjamin Ebert, Richard Stone, Donald Kufe, Gordon J. Freeman, Jacalyn Rosenblatt, David Avigan   +23 more
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A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report

Frontiers in Immunology, 2021
BackgroundIt was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade.
Fangyuan Zhang, Jieying Zhang, Lei Zhao, Menglan Zhai, Tao Zhang, Dandan Yu   +5 more
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PD-1 and LAG-3 blockade improve anti-tumor vaccine efficacy

OncoImmunology, 2021
Concurrent blockade of different checkpoint receptors, notably PD-1 and CTLA-4, elicits greater anti-tumor activity for some tumor types, and the combination of different checkpoint receptor inhibitors is an active area of clinical research.
Christopher D. Zahm, Jena E Moseman, Lauren E. Delmastro, Douglas G. Mcneel   +3 more
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Immune checkpoint blockade therapy [PDF]

Journal of Allergy and Clinical Immunology, 2018
Immune checkpoints are accessory molecules that either promote or inhibit T-cell activation. Two inhibitory molecules, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), got high attention, as inhibition of CTLA-4 or PD-1 signaling provides the first immune therapy that significantly improves the survival of patients ...
Thomas, Wieder, Thomas, Eigentler, Ellen, Brenner, Martin, Röcken   +3 more
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Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40

Nature Communications, 2021
Glioblastomas are generally resistant to treatment with immune checkpoint inhibitors. Here the authors show that IL6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune ...
Fan Yang, Zhenqiang He, Hao Duan, Duo Zhang, Juehui Li, Huijuan Yang, Jay F. Dorsey, Wei Zou, S. Ali Nabavizadeh, Stephen J. Bagley, Kalil Abdullah, Steven Brem, Lin Zhang, Xiaowei Xu, Katelyn T. Byrne, Robert H. Vonderheide, Yanqing Gong, Yi Fan   +17 more
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Epitherapy and immune checkpoint blockade: using epigenetic reinvigoration of exhausted and dysfunctional T cells to reimburse immunotherapy response

BMC Immunology, 2020
Background Cancer cells subvert natural immunosuppression by upregulating the expression of checkpoint proteins and their ligands. For example, tumor cells expressing programmed death-ligand 1 (PD-L1) induce immune cell tolerance to cancers, thereby ...
Isabella McGoverne, Jenny Dunn, Jacob Batham, Wen Juan Tu, Jeremy Chrisp, Sudha Rao   +5 more
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Enhancing the efficacy of immunotherapy using radiotherapy

Clinical & Translational Immunology, 2020
Recent clinical breakthroughs in cancer immunotherapy, especially with immune checkpoint blockade, offer great hope for cancer sufferers – and have greatly changed the landscape of cancer treatment.
Synat Keam, Suki Gill, Martin A Ebert, Anna K Nowak, Alistair M Cook   +4 more
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Combined immune checkpoint blockade increases CD8+CD28+PD-1+ effector T cells and provides a therapeutic strategy for patients with neuroblastoma

OncoImmunology, 2021
Immune checkpoint therapy has resulted in minimal clinical response in many pediatric cancers. We sought to understand the influence of immune checkpoint inhibition using anti-PD-1 and anti-CTLA-4 antibodies individually, in combination, and after ...
Soheila Shirinbak, Randall Y. Chan, Shilpa Shahani, Sakunthala Muthugounder, Rebekah Kennedy, Long T. Hung, G. Esteban Fernandez, Michael D. Hadjidaniel, Babak Moghimi, Michael A. Sheard, Alan L. Epstein, Muller Fabbri, Hiroyuki Shimada, Shahab Asgharzadeh   +13 more
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