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Article ; Online: Correction: Musa et al. An Electrochemical Screen-Printed Sensor Based on Gold-Nanoparticle-Decorated Reduced Graphene Oxide-Carbon Nanotubes Composites for the Determination of 17-β Estradiol.

Musa, Auwal M / Kiely, Janice / Luxton, Richard / Honeychurch, Kevin C

2023 Volume 13, Issue 7

Abstract: In the original publication [ ... ]. ...

Abstract	In the original publication [...].
Language	English
Publishing date	2023-07-24
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios13070756
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Article ; Online: An Electrochemical Screen-Printed Sensor Based on Gold-Nanoparticle-Decorated Reduced Graphene Oxide-Carbon Nanotubes Composites for the Determination of 17-β Estradiol.

Musa, Auwal M / Kiely, Janice / Luxton, Richard / Honeychurch, Kevin C

Biosensors

2023 Volume 13, Issue 4

Abstract: In this study, a screen-printed electrode (SPE) modified with gold-nanoparticle-decorated reduced graphene oxide-carbon nanotubes (rGO-AuNPs/CNT/SPE) was used for the determination of estradiol (E2). The AuNPs were produced through an eco-friendly method ...

Abstract	In this study, a screen-printed electrode (SPE) modified with gold-nanoparticle-decorated reduced graphene oxide-carbon nanotubes (rGO-AuNPs/CNT/SPE) was used for the determination of estradiol (E2). The AuNPs were produced through an eco-friendly method utilising plant extract, eliminating the need for severe chemicals, and remove the requirements of sophisticated fabrication methods and tedious procedures. In addition, rGO-AuNP serves as a dispersant for the CNT to improve the dispersion stability of CNTs. The composite material, rGO-AuNPs/CNT, underwent characterisation through scanning electron microscopy (SEM), ultraviolet-visible absorption spectroscopy (UV-vis), Fourier-transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). The electrochemical performance of the modified SPE for estradiol oxidation was characterised using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The rGO-AuNPs/CNT/SPE exhibited a notable improvement compared to bare/SPE and GO-CNT/SPE, as evidenced by the relative peak currents. Additionally, we employed a baseline correction algorithm to accurately adjust the sensor response while eliminating extraneous background components that are typically present in voltammetric experiments. The optimised estradiol sensor offers linear sensitivity from 0.05-1.00 µM, with a detection limit of 3 nM based on three times the standard deviation (3δ). Notably, this sensing approach yields stable, repeatable, and reproducible outcomes. Assessment of drinking water samples indicated an average recovery rate of 97.5% for samples enriched with E2 at concentrations as low as 0.5 µM%, accompanied by only a modest coefficient of variation (%CV) value of 2.7%.
MeSH term(s)	Nanotubes, Carbon/chemistry ; Gold/chemistry ; Metal Nanoparticles/chemistry ; Estradiol ; Graphite/chemistry ; Electrodes ; Electrochemical Techniques/methods
Chemical Substances	Nanotubes, Carbon ; graphene oxide ; Gold (7440-57-5) ; Estradiol (4TI98Z838E) ; Graphite (7782-42-5)
Language	English
Publishing date	2023-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios13040491
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Article: Radiotherapy-Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?

Romano, Erminia / Honeychurch, Jamie / Illidge, Timothy M

Cancers

2021 Volume 13, Issue 3

Abstract: Radiotherapy (RT) is highly effective at directly killing tumor cells and plays an important part in cancer treatments being delivered to around 50% of all cancer patients. The additional immunomodulatory properties of RT have been investigated, and if ... ...

Abstract	Radiotherapy (RT) is highly effective at directly killing tumor cells and plays an important part in cancer treatments being delivered to around 50% of all cancer patients. The additional immunomodulatory properties of RT have been investigated, and if exploited effectively, have the potential to further improve the efficacy of RT and cancer outcomes. The initial results of combining RT with immunomodulatory agents have generated promising data in pre-clinical studies, which has in turn led to a large number of RT and immunotherapy clinical trials. The overarching aim of these combinations is to enhance anti-tumor immune responses and improve responses rates and patient outcomes. In order to maximize this undoubted opportunity, there remain a number of important questions that need to be addressed, including: (i) the optimal RT dose and fractionation schedule; (ii) the optimal RT target volume; (iii) the optimal immuno-oncology (IO) agent(s) to partner with RT; (iv) the optimal site(s)/route(s) of administration of IO agents; and finally, the optimal RT schedule. In this review, we will summarize progress to date and identify current gaps in knowledge that need to be addressed in order to facilitate effective clinical translation of RT and IO agent combinations.
Language	English
Publishing date	2021-01-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13030457
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Article: The influence of radiation in the context of developing combination immunotherapies in cancer.

Honeychurch, Jamie / Illidge, Timothy M

Therapeutic advances in vaccines and immunotherapy

2018 Volume 5, Issue 6, Page(s) 115–122

Abstract: In addition to tumouricidal activity, radiotherapy is now recognized to display potent immunostimulatory properties that can contribute to the generation of anti-cancer immune responses. Treatment with radiation can induce a variety of pro-immunogenic ... ...

Abstract	In addition to tumouricidal activity, radiotherapy is now recognized to display potent immunostimulatory properties that can contribute to the generation of anti-cancer immune responses. Treatment with radiation can induce a variety of pro-immunogenic and phenotypic changes in malignant cells, and recalibrate the immune contexture of the tumour microenvironment, leading to enhanced activation of the innate immune system, and priming of tumour-specific T-cell immunity. The immune-dependent effects of radiotherapy provide a sound rationale for the development of combination strategies, whereby the immunomodulatory properties of radiation can be exploited to augment the activity of immunotherapeutic agents. Encouraged by the recent success of breakthrough therapies such as immune checkpoint blockade, and a wealth of experimental data demonstrating the efficacy of radiotherapy and immunotherapy combinations, the clinical potential of this approach is now being explored in numerous trials. Successful translation will require careful consideration of the most suitable dose and fractionation of radiation, choice of immunotherapy and optimal sequencing and scheduling regimen. Immunological control of cancer is now becoming a clinical reality. There is considerable optimism that the development of effective radiotherapy and immunotherapy combinations with the capacity to induce durable, systemic immunity will further enhance patient outcome and transform the future management of cancer.
Language	English
Publishing date	2018-01-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2970613-0
ISSN	2515-1363 ; 2515-1355
ISSN (online)	2515-1363
ISSN	2515-1355
DOI	10.1177/2051013617750561
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Article ; Online: Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations.

Colton, Madyson / Cheadle, Eleanor J / Honeychurch, Jamie / Illidge, Tim M

Radiation oncology (London, England)

2020 Volume 15, Issue 1, Page(s) 254

Abstract: Radiotherapy (RT) is a highly effective anti-cancer therapy delivered to around 50-60% of patients. It is part of therapy for around 40% of cancer patients who are cured of their disease. Until recently, the focus of this anti-tumour efficacy has been on ...

Abstract	Radiotherapy (RT) is a highly effective anti-cancer therapy delivered to around 50-60% of patients. It is part of therapy for around 40% of cancer patients who are cured of their disease. Until recently, the focus of this anti-tumour efficacy has been on the direct tumour cytotoxicity and RT-induced DNA damage. Recently, the immunomodulatory effects of RT on the tumour microenvironment have increasingly been recognized. There is now intense interest in potentially using RT to induce an anti-tumour immune response, which has led to rethinking into how the efficacy of RT could be further enhanced. Following the breakthrough of immune check point inhibitors (ICIs), a new era of immuno-oncology (IO) agents has emerged and established immunotherapy as a routine part of cancer treatment. Despite ICI improving outcomes in many cancer types, overall durable responses occur in only a minority of patients. The immunostimulatory effects of RT make combinations with ICI attractive to potentially amplify anti-tumour immunity resulting in increased tumour responses and improved outcomes. In contrast, tumours with profoundly immunosuppressive tumour microenvironments, dominated by myeloid-derived cell populations, remain a greater clinical challenge and RT may potentially further enhance the immunosuppression. To harness the full potential of RT and IO agent combinations, further insights are required to enhance our understanding of the role these immunosuppressive myeloid populations play, how RT influences these populations and how they may be therapeutically manipulated in combination with RT to improve outcomes further. These are exciting times with increasing numbers of IO targets being discovered and IO agents undergoing clinical evaluation. Multidisciplinary research collaborations will be required to establish the optimal parameters for delivering RT (target volume, dose and fractionation) in combination with IO agents, including scheduling to achieve maximal therapeutic efficacy.
MeSH term(s)	Combined Modality Therapy ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/radiotherapy ; T-Lymphocytes/physiology ; Tumor Microenvironment
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2020-11-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2224965-5
ISSN	1748-717X ; 1748-717X
ISSN (online)	1748-717X
ISSN	1748-717X
DOI	10.1186/s13014-020-01678-1
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Article ; Online: Toll-Like Receptor Agonists and Radiation Therapy Combinations: An Untapped Opportunity to Induce Anticancer Immunity and Improve Tumor control.

Walshaw, Richard C / Honeychurch, Jamie / Choudhury, Ananya / Illidge, Timothy M

International journal of radiation oncology, biology, physics

2020 Volume 108, Issue 1, Page(s) 27–37

Abstract: The premise that therapies targeting immune checkpoints can enhance radiation therapy (RT)-induced antitumor immunity is being explored rigorously in the preclinical setting, and early clinical trials testing this hypothesis are beginning to report. ... ...

Abstract	The premise that therapies targeting immune checkpoints can enhance radiation therapy (RT)-induced antitumor immunity is being explored rigorously in the preclinical setting, and early clinical trials testing this hypothesis are beginning to report. Although such approaches might prove efficacious in certain settings, it is likely that many tumor types, particularly those that have a deeply immune-suppressed microenvironment with little or no T cell infiltration, will require alternative approaches. Thus, there is now considerable drive to develop novel immune modulatory therapies that target other areas of the cancer immunity cycle. Toll-like receptors (TLRs) are expressed on sentinel immune cells and play a key role in the host defense against invading pathogens. Innate sensing via TLR-mediated detection of pathogen-derived molecular patterns can lead to maturation of antigen-presenting cells and downstream activation of adaptive immunity. After demonstrating promising efficacy in preclinical studies, drugs that stimulate TLR have been approved for use clinically, albeit to a limited extent. There is a growing body of preclinical evidence that novel agonists targeting TLR3, TLR7/8, or TLR9 in combination with RT might lead to enhanced antitumor immunity. Mechanistic studies have revealed that TLR agonists enhance dendritic cell-mediated T cell priming after RT, in some cases leading to the generation of systemic antitumor immunity and immune memory. In this report, we describe results from preclinical studies that advocate the strategy of combining RT with TLR agonists, discuss reported mechanisms of action, and explore the exciting opportunities of how this approach may be successfully translated into clinical practice.
MeSH term(s)	Animals ; Combined Modality Therapy ; Humans ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/radiotherapy ; Toll-Like Receptors/agonists
Chemical Substances	Toll-Like Receptors
Language	English
Publishing date	2020-04-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2020.04.020
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Article: Stromal cell inhibition of anti-CD20 antibody mediated killing of B-cell malignancies.

Fagnano, Ester / Pendharkar, Swati / Colton, Madyson / Jones, Philip N / Sallan, Marta Crespi / Klymenko, Tetyana / Braun, Andrejs / Klein, Christian / Honeychurch, Jamie / Cheadle, Eleanor J / Illidge, Timothy M

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1270398

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1270398
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Article ; Online: Radiotherapy transiently reduces the sensitivity of cancer cells to lymphocyte cytotoxicity.

Tuomela, Karoliina / Mukherjee, Debayan / Ambrose, Ashley R / Harikrishnan, Ashish / Mole, Holly / Hurlstone, Adam / Önfelt, Björn / Honeychurch, Jamie / Davis, Daniel M

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 3

Abstract: The impact of radiotherapy on the interaction between immune cells and cancer cells is important not least because radiotherapy can be used alongside immunotherapy as a cancer treatment. Unexpectedly, we found that X-ray irradiation of cancer cells ... ...

Abstract	The impact of radiotherapy on the interaction between immune cells and cancer cells is important not least because radiotherapy can be used alongside immunotherapy as a cancer treatment. Unexpectedly, we found that X-ray irradiation of cancer cells induced significant resistance to natural killer (NK) cell killing. This was true across a wide variety of cancer-cell types as well as for antibody-dependent cellular cytotoxicity. Resistance appeared 72 h postirradiation and persisted for 2 wk. Resistance could also occur independently of radiotherapy through pharmacologically induced cell-cycle arrest. Crucially, multiple steps in NK-cell engagement, synapse assembly, and activation were unaffected by target cell irradiation. Instead, radiotherapy caused profound resistance to perforin-induced calcium flux and lysis. Resistance also occurred to a structurally similar bacterial toxin, streptolysin O. Radiotherapy did not affect the binding of pore-forming proteins at the cell surface or membrane repair. Rather, irradiation instigated a defect in functional pore formation, consistent with phosphatidylserine-mediated perforin inhibition. In vivo, radiotherapy also led to a significant reduction in NK cell-mediated clearance of cancer cells. Radiotherapy-induced resistance to perforin also constrained chimeric antigen receptor T-cell cytotoxicity. Together, these data establish a treatment-induced resistance to lymphocyte cytotoxicity that is important to consider in the design of radiotherapy-immunotherapy protocols.
MeSH term(s)	Antibody-Dependent Cell Cytotoxicity ; Bacterial Proteins ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cytotoxicity, Immunologic ; Humans ; Immunotherapy ; Killer Cells, Natural/immunology ; Neoplasms/metabolism ; Perforin/metabolism ; Radiotherapy ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Chimeric Antigen/metabolism ; Streptolysins
Chemical Substances	Bacterial Proteins ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; Streptolysins ; streptolysin O ; Perforin (126465-35-8)
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2111900119
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Article ; Online: Immunomodulation by radiotherapy in tumour control and normal tissue toxicity.

Cytlak, Urszula M / Dyer, Douglas P / Honeychurch, Jamie / Williams, Kaye J / Travis, Mark A / Illidge, Timothy M

Nature reviews. Immunology

2021 Volume 22, Issue 2, Page(s) 124–138

Abstract: Radiotherapy (RT) is a highly effective anticancer treatment that is delivered to more than half of all patients with cancer. In addition to the well-documented direct cytotoxic effects, RT can have immunomodulatory effects on the tumour and surrounding ... ...

Abstract	Radiotherapy (RT) is a highly effective anticancer treatment that is delivered to more than half of all patients with cancer. In addition to the well-documented direct cytotoxic effects, RT can have immunomodulatory effects on the tumour and surrounding tissues. These effects are thought to underlie the so-called abscopal responses, whereby RT generates systemic antitumour immunity outside the irradiated tumour. The full scope of these immune changes remains unclear but is likely to involve multiple components, such as immune cells, the extracellular matrix, endothelial and epithelial cells and a myriad of chemokines and cytokines, including transforming growth factor-β (TGFβ). In normal tissues exposed to RT during cancer therapy, acute immune changes may ultimately lead to chronic inflammation and RT-induced toxicity and organ dysfunction, which limits the quality of life of survivors of cancer. Here we discuss the emerging understanding of RT-induced immune effects with particular focus on the lungs and gut and the potential immune crosstalk that occurs between these tissues.
MeSH term(s)	Humans ; Immunity ; Immunomodulation ; Immunotherapy ; Neoplasms ; Quality of Life
Language	English
Publishing date	2021-07-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-021-00568-1
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The CD40 agonist HERA-CD40L results in enhanced activation of antigen presenting cells, promoting an anti-tumor effect alone and in combination with radiotherapy.

Frankish, Jamie / Mukherjee, Debayan / Romano, Erminia / Billian-Frey, Katharina / Schröder, Matthias / Heinonen, Karl / Merz, Christian / Redondo Müller, Mauricio / Gieffers, Christian / Hill, Oliver / Thiemann, Meinolf / Honeychurch, Jamie / Illidge, Tim / Sykora, Jaromir

Frontiers in immunology

2023 Volume 14, Page(s) 1160116

Abstract: Introduction: The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially excellent targets for modulation which ... ...

Abstract	Introduction: The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially excellent targets for modulation which result in specific anti-tumor immune responses. CD40 is a member of the TNFRSF and several clinical therapies are under development. CD40 signaling plays a pivotal role in regulating the immune system from B cell responses to myeloid cell driven activation of T cells. The CD40 signaling axis is well characterized and here we compare next generation HERA-Ligands to conventional monoclonal antibody based immune modulation for the treatment of cancer. Methods & results: HERA-CD40L is a novel molecule that targets CD40 mediated signal transduction and demonstrates a clear mode of action in generating an activated receptor complex via recruitment of TRAFs, cIAP1, and HOIP, leading to TRAF2 phosphorylation and ultimately resulting in the enhanced activation of key inflammatory/survival pathway and transcription factors such asNFkB, AKT, p38, ERK1/2, JNK, and STAT1 in dendritic cells. Furthermore, HERA-CD40L demonstrated a strong modulation of the tumor microenvironment (TME) via the increase in intratumoral CD8+ T cells and the functional switch from pro-tumor macrophages (TAMs) to anti-tumor macrophages that together results in a significant reduction of tumor growth in a CT26 mouse model. Furthermore, radiotherapy which may have an immunosuppressive modulation of the TME, was shown to have an immunostimulatory effect in combination with HERA-CD40L. Radiotherapy in combination with HERA-CD40L treatment resulted in an increase in detected intratumoral CD4+/8+ T cells compared to RT alone and, additionally, the repolarization of TAMs was also observed, resulting in an inhibition of tumor growth in a TRAMP-C1 mouse model. Discussion: Taken together, HERA-CD40L resulted in activating signal transduction mechanisms in dendritic cells, resulting in an increase in intratumoral T cells and manipulation of the TME to be pro-inflammatory, repolarizing M2 macrophages to M1, enhancing tumor control.
MeSH term(s)	Animals ; Mice ; CD40 Ligand ; CD40 Antigens ; Antigen-Presenting Cells ; Macrophages ; Neoplasms/radiotherapy ; Disease Models, Animal ; Tumor Microenvironment
Chemical Substances	CD40 Ligand (147205-72-9) ; CD40 Antigens
Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1160116
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