ORCID Profile
0000-0002-4580-3443
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Imperial College London
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Publisher: eLife Sciences Publications, Ltd
Date: 27-10-2014
DOI: 10.7554/ELIFE.03180
Abstract: The co-stimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming, we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.
Publisher: Cold Spring Harbor Laboratory
Date: 24-11-2021
DOI: 10.1101/2021.11.24.469855
Abstract: The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis. The T cell paracortical zone is a major site of macrophage efferocytosis of apoptotic cells, but key factors controlling this niche are undefined. Here we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Macrophages co-localised with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that most reticular cells expressed master macrophage regulator CSF1. Functional assays showed that CSF1R signalling was sufficient to support macrophage development. In the presence of LPS, FRCs underwent a mechanistic switch and maintained support through CSF1R-independent mechanisms. These effects were conserved between mouse and human systems. Rapid loss of macrophages and monocytes from LNs was observed upon genetic ablation of FRCs. These data reveal a critically important role for FRCs in the creation of the parenchymal macrophage niche within LNs.
Publisher: Elsevier BV
Date: 2020
Publisher: Springer International Publishing
Date: 2018
DOI: 10.1007/978-3-319-78127-3_6
Abstract: The tumor microenvironment comprises a mass of heterogeneous cell types, including immune cells, endothelial cells, and fibroblasts, alongside cancer cells. It is increasingly becoming clear that the development of this support niche is critical to the continued uncontrolled growth of the cancer. The tumor microenvironment contributes to the maintenance of cancer stemness and also directly promotes angiogenesis, invasion, metastasis, and chronic inflammation. In this chapter, we describe on the role of fibroblasts, specifically termed cancer-associated fibroblasts (CAFs), in the promotion and maintenance of cancers. CAFs have a multitude of effects on the growth and maintenance of cancer, and here we focus on their roles in modulating immune cells and responses CAFs both inhibit immune cell access to the tumor microenvironment and inhibit their functions within the tumor. Finally, we describe the potential modulation of CAF function as an adjunct to bolster the effectiveness of cancer immunotherapies.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.COI.2017.03.001
Abstract: Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ. Further, distinct populations of stromal cells underpin the delicate spatial organization of immune cells within the germinal centre. Because of this, the interactions between immune cells and stromal cells in secondary lymphoid organs are fundamental to the germinal centre response. Herein we review how this unique relationship leads to effective germinal centre responses.
Publisher: Elsevier
Date: 2016
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-05-2022
DOI: 10.1126/SCIIMMUNOL.ABK0018
Abstract: The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center (GC) response, which generates long-lived antibody-secreting cells that protect against (re)infection. Despite intensive investigation, the primary cellular defect underlying impaired GCs in aging has not been identified. Here, we used heterochronic parabiosis to demonstrate that GC formation was dictated by the age of the lymph node (LN) microenvironment rather than the age of the immune cells. Lymphoid stromal cells are a key determinant of the LN microenvironment and are also an essential component underpinning GC structure and function. Using mouse models, we demonstrated that mucosal adressin cell adhesion molecule–1 (MAdCAM-1)–expressing lymphoid stromal cells were among the first cells to respond to NP-KLH + Alum immunization, proliferating and up-regulating cell surface proteins such as podoplanin and cell adhesion molecules. This response was essentially abrogated in aged mice. By targeting TLR4 using adjuvants, we improved the MAdCAM-1 + stromal cell response to immunization. This correlated with improved GC responses in both younger adult and aged mice, suggesting a link between stromal cell responses to immunization and GC initiation. Using bone marrow chimeras, we also found that MAdCAM-1 + stromal cells could respond directly to TLR4 ligands. Thus, the age-associated defect in GC and stromal cell responses to immunization can be targeted to improve vaccines in older people.
Publisher: Proceedings of the National Academy of Sciences
Date: 04-08-2014
Abstract: The balance between the retention of lymphocytes in lymph nodes and their exit is a key factor determining clonal burst size, differentiation, and the efficacy of pathogen clearance. Currently, it is understood that naïve and activated T cells regulate their migration using a similar system, that is, balancing CC chemokine receptor (CCR)7-mediated retention signals against Sphingosine-1 phosphate receptor-1 (S1PR1)-mediated exit signals. This study utilizes a mouse model to selectively deplete the cellular source of CCR7 ligands, the fibroblastic reticular cells, before or during viral infection. The study concludes that while retention of naïve lymphocytes does depend on the fibroblastic reticular cell, it may be a cell-autonomous response of activated T cells that allows them to determine in a cell-intrinsic manner the magnitude of clonal expansion.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6510989.V1
Abstract: Abstract Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [ sup /sup F]FDG uptake and MRI measurement of hyperpolarized [1- sup /sup C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6- sup /sup C sub /sub ]glucose and measuring sup /sup C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1- sup /sup C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [ sup /sup F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [ sup /sup F]FDG uptake by infiltrating immune cells. Quantification of [ sup /sup F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b sup + /sup /CD45 sup + /sup macrophages as the most [ sup /sup F]FDG-avid cell type present, yet they represented % of the cells present in the tumors and could not explain the failure of [ sup /sup F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1- sup /sup C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [ sup /sup F]FDG uptake. Significance: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1- sup /sup C]pyruvate metabolism versus PET measurement of sup /sup F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death. /
Publisher: Proceedings of the National Academy of Sciences
Date: 29-08-2011
Abstract: Although the simultaneous engagement of multiple effector mechanisms is thought to characterize optimal CD8 + T-cell immunity and facilitate pathogen clearance, the differentiation pathways leading to the acquisition and maintenance of such polyfunctional activity are not well understood. Division-dependent profiles of effector molecule expression for virus-specific T cells are analyzed here by using a combination of carboxyfluorescein succinimidyl ester dilution and intracellular cytokine staining subsequent to T-cell receptor ligation. The experiments show that, although the majority of naive CD8 + T-cell precursors are preprogrammed to produce TNF-α soon after stimulation and a proportion make both TNF-α and IL-2, the progressive acquisition of IFN-γ expression depends on continued lymphocyte proliferation. Furthermore, the extensive ision characteristic of differentiation to peak effector activity is associated with the progressive dominance of IFN-γ and the concomitant loss of polyfunctional cytokine production, although this is not apparent for long-term CD8 + T-cell memory. Such proliferation-dependent variation in cytokine production appears tied to the epigenetic signatures within the ifnG and tnfA proximal promoters. Specifically, those cytokine gene loci that are rapidly expressed following antigen stimulation at different stages of T-cell differentiation can be shown (by ChIP) to have permissive epigenetic and RNA polymerase II docking signatures. Thus, the dynamic changes in cytokine profiles for naive, effector, and memory T cells are underpinned by specific epigenetic landscapes that regulate responsiveness following T-cell receptor ligation.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22421690
Abstract: Figure S1. Timeline of injections and imaging for the main treatment-response study. Figure S2. Tumor volume measurements for (a) Colo205 and (b) MDA-MB-231 tumors (b & e) before and (c & f) 24 h after MEDI3039 treatment. Figure S3. Confirmation that [18F]FDG uptake was similar before and 24 h after treatment. Ex les of autoradiography of whole-body axial sections of Colo205 tumor-bearing mice (the tumors are outlined) before (a - c) and 24 h after treatment (d - f). Figure S4. Dynamic contrast enhanced MRI measurements of perfusion in Colo205 tumors before and 24 h after treatment with MEDI3039. Figure S5. RadioHPLC measurements of [18F]FDG metabolism in Colo205 tumors 24 h after control (drug vehicle) or MEDI3039 treatment. Table S1. Colo205 mice that underwent fluorescence, bioluminescence, hyperpolarized MR and PET-CT imaging and reasons for their exclusion. Table S2. MDA-MB-231 mice that underwent fluorescence, bioluminescence, hyperpolarized MR and PET-CT imaging and reasons for their exclusion. Table S3. Antibodies used for Western blotting. Table S4. Expression of the transporters and enzymes and the activities of the enzymes involved in [18F]FDG and [1-13C]pyruvate uptake and metabolism in Colo205 tumors.
Publisher: Frontiers Media SA
Date: 28-09-2018
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
DOI: 10.1038/S41467-019-09434-0
Abstract: Several tolerance checkpoints exist throughout B cell development to control autoreactive B cells and prevent the generation of pathogenic autoantibodies. FcγRIIb is an Fc receptor that inhibits B cell activation and, if defective, is associated with autoimmune disease, yet its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of FcγRIIb enhances the deletion and anergy of autoreactive immature B cells, but in contrast promotes autoreactive B cell expansion in the germinal center and serum autoantibody production, even in response to exogenous, non-self antigens. Our data thus show that FcγRIIb has opposing effects on pre-immune and post-immune tolerance checkpoints, and suggest that B cell tolerance requires the control of bystander germinal center B cells with low or no affinity for the immunizing antigen.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2023
Publisher: Wiley
Date: 25-09-2019
Abstract: The mechanistic basis of memory T-cell development is poorly defined. Phenotypic markers that define precursors at effector stages have been characterized for acute systemic infections with high antigen load. We asked whether such markers can identify memory precursors from early effectors (d6) to late memory (>d500) for two immunodominant CD8(+) responses during the course of a localized low-load influenza infection in mice. CD8(+) T cells stained with the D(b) NP(366) and D(b) PA(224) tetramers were characterized as IL-7Rα(hi) , IL-7Rα(hi) CD62L(hi) or IL-7Rα(hi) KLRG1(lo) . While the D(b) NP(366) - and D(b) PA(224) -specific responses were comparable in size, decay kinetics and memory precursor frequency, their expansion characteristics differed. This correlated with a ergence in the IL-7Rα(hi) , IL-7Rα(hi) CD62L(hi) and IL-7Rα(hi) KLRG1(lo) phenotypes on effector, but not naïve, CD8(+) populations. That effect was abrogated by priming with viruses engineered to present equivalent levels of NP(366) and PA(224) peptides, indicating that memory phenotypes reflect early antigenic experience rather than memory potential. Thus, the IL-7Rα(hi) KLRG1(lo) phenotype had a poor predictive value in identifying memory precursors in the spleen and at the site of infection. Greater consistency in influenza-specific IL-7Rα(hi) KLRG1(lo) CD8(+) T-cell numbers was found in draining lymph nodes, suggesting that this may be the preferential site for memory establishment and maintenance following localized virus infections.
Publisher: BMJ
Date: 06-2016
Publisher: Wiley
Date: 12-07-2023
Abstract: The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co‐localized with FRCs in human LNs, and murine single‐cell RNA‐sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.
Publisher: Wiley
Date: 02-2007
Abstract: The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-gamma production by NK cells and T lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8+ T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40(-/-)) or IL-18 (IL-18(-/-)) genes were infected with an influenza A virus and the characteristics of the resultant epitope-specific CD8+ T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8+ T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-gamma, TNF-alpha, and IL-2 by epitope-specific CD8+ T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8+ T cells for the efficient clearance of influenza virus from the lungs of infected mice.
Publisher: Elsevier
Date: 2016
Publisher: Rockefeller University Press
Date: 19-07-2019
DOI: 10.1084/JEM.20181705
Abstract: The induction of adaptive immunity is dependent on the structural organization of LNs, which is in turn governed by the stromal cells that underpin LN architecture. Using a novel fate-mapping mouse model, we trace the developmental origin of mesenchymal LN stromal cells (mLNSCs) to a previously undescribed embryonic fibroblast activation protein-α (FAP)+ progenitor. FAP+ cells of the LN anlagen express lymphotoxin β receptor (LTβR) and vascular cell adhesion molecule (VCAM), but not intercellular adhesion molecule (ICAM), suggesting they are early mesenchymal lymphoid tissue organizer (mLTo) cells. Clonal labeling shows that FAP+ progenitors locally differentiate into mLNSCs. This process is also coopted in nonlymphoid tissues in response to infection to facilitate the development of tertiary lymphoid structures, thereby mimicking the process of LN ontogeny in response to infection.
Publisher: The American Association of Immunologists
Date: 12-2011
Abstract: High-avidity interactions between TCRs and peptide + class I MHC (pMHCI) epitopes drive CTL activation and expansion. Intriguing questions remain concerning the constraints determining optimal TCR MHCI binding. The present analysis uses the TCR transgenic OT-I model to assess how varying profiles of TCR MHCI avidity influence naive CTL proliferation and the acquisition of effector function following exposure to the cognate H-2Kb/OVA257–264 (SIINFEKL) epitope and to mutants provided as peptide or in engineered influenza A viruses. Stimulating naive OT-I CD8+ T cells in vitro with SIINFEKL induced full CTL proliferation and differentiation that was largely independent of any need for costimulation. By contrast, in vitro activation with the low-affinity EIINFEKL or SIIGFEKL ligands depended on the provision of IL-2 and other costimulatory signals. Importantly, although they did generate potent endogenous responses, infection of mice with influenza A viruses expressing these same OVA257 variants failed to induce the activation of adoptively transferred naive OT-I CTLps, an effect that was only partially overcome by priming with a lipopeptide vaccine. Subsequent structural and biophysical analysis of H2-KbOVA257, H2-KbE1, and H2-KbG4 established that these variations introduce small changes at the pMHCI interface and decrease epitope stability in ways that would likely impact cell surface presentation and recognition. Overall, it seems that there is an activation threshold for naive CTLps, that minimal alterations in peptide sequence can have profound effects, and that the antigenic requirements for the in vitro and in vivo induction of CTL proliferation and effector function differ substantially.
Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism
Date: 03-2017
Publisher: Research Square Platform LLC
Date: 15-06-2022
DOI: 10.21203/RS.3.RS-1733421/V1
Abstract: Vaccination generates long-lived antibody-mediated immunity against (re-)infection. This humoral immunity is derived from memory B cells and long-lived antibody-secreting plasma cells via the germinal centre (GC) response. The magnitude and quality of the GC response declines with age, resulting in poor vaccine-induced immunity in older in iduals, but the causal factor/s of this age-related decline are unknown. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. We identified that the spatial organisation of the GC is altered in ageing, with CXCR4-mediated mislocalisation of T follicular helper (Tfh) cells in the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. By modulating the positioning of Tfh cells in vivo, we found that Tfh cell polarisation is critical for the quality of the antibody response, and, surprisingly, for the expansion of the FDC network upon immunisation. The smaller GC responses and defective FDC expansion in ageing were corrected by provision of Tfh cells that co-localise with FDCs via CXCR5:CXCL13-mediated interaction. This demonstrates that the age-dependent defects in the GC response are reversible and shows that Tfh cells have a dual role in B cell help and facilitating stromal cell responses to vaccines.
Publisher: Frontiers Media SA
Date: 2012
Publisher: The American Association of Immunologists
Date: 12-2009
Abstract: The role of chromatin remodeling and histone posttranslational modifications and how they are integrated to control gene expression during the acquisition of cell-specific functions is poorly understood. We show here that following in vitro activation of CD4+ and CD8+ T lymphocytes, both cell types show rapid histone H3 loss at the granzyme B (gzmB) proximal promoter region. However, despite the gzmB proximal promoter being remodeled in both T cell subsets, only CD8+ T cells express high levels of gzmB and display a distinct pattern of key epigenetic marks, notably differential H3 acetylation and methylation. These data suggest that for high levels of transcription to occur a distinct set of histone modifications needs to be established in addition to histone loss at the proximal promoter of gzmB.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2023
DOI: 10.1038/S41590-023-01519-9
Abstract: The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older in iduals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (T FH ) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that T FH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of T FH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that T FH cells support stromal cell responses to vaccines.
Publisher: Rockefeller University Press
Date: 05-02-2019
DOI: 10.1084/JEM.20181216
Abstract: Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
Publisher: Public Library of Science (PLoS)
Date: 08-09-2017
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.IMMUNI.2014.12.009
Abstract: The mechanism by which regulatory T cells control the germinal center response is unknown. In this issue of Immunity, Wing et al. (2014) and Sage et al. (2014) demonstrate that CTLA-4 is a critical effector molecule used by regulatory T cells to control the germinal center.
Publisher: American Association for Cancer Research (AACR)
Date: 15-07-2019
DOI: 10.1158/0008-5472.CAN-19-0182
Abstract: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Springer Science and Business Media LLC
Date: 19-08-2021
Publisher: The American Association of Immunologists
Date: 13-01-2010
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.07.082255
Abstract: The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center response, which generates long-lived antibody-secreting cells that provide protection against (re)infection. Despite intensive investigation into the effect of age on the lymphoid compartment, the primary cellular defect that causes impaired germinal centers in aging has not been identified. Herein we demonstrate that aging reduces the capacity of germinal center-associated stromal cells to respond to vaccination. Heterochronic parabiosis and mathematical modeling demonstrate that a poor stromal cell response limits the size of the germinal center. This study reveals that age-associated defects in stromal cells are a significant barrier to efficacious vaccine responses in older in iduals.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Oxford University Press (OUP)
Date: 2021
Abstract: The generation of high-affinity long-lived antibody responses is dependent on the differentiation of plasma cells and memory B cells, which are themselves the product of the germinal centre (GC) response. The GC forms in secondary lymphoid organs in response to antigenic stimulation and is dependent on the coordinated interactions between many types of leucocytes. These leucocytes are brought together on an interconnected network of specialized lymphoid stromal cells, which provide physical and chemical guidance to immune cells that are essential for the GC response. In this review we will highlight recent advancements in lymphoid stromal cell immunobiology and their role in regulating the GC, and discuss the contribution of lymphoid stromal cells to age-associated immunosenescence.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22421690.V1
Abstract: Figure S1. Timeline of injections and imaging for the main treatment-response study. Figure S2. Tumor volume measurements for (a) Colo205 and (b) MDA-MB-231 tumors (b & e) before and (c & f) 24 h after MEDI3039 treatment. Figure S3. Confirmation that [18F]FDG uptake was similar before and 24 h after treatment. Ex les of autoradiography of whole-body axial sections of Colo205 tumor-bearing mice (the tumors are outlined) before (a - c) and 24 h after treatment (d - f). Figure S4. Dynamic contrast enhanced MRI measurements of perfusion in Colo205 tumors before and 24 h after treatment with MEDI3039. Figure S5. RadioHPLC measurements of [18F]FDG metabolism in Colo205 tumors 24 h after control (drug vehicle) or MEDI3039 treatment. Table S1. Colo205 mice that underwent fluorescence, bioluminescence, hyperpolarized MR and PET-CT imaging and reasons for their exclusion. Table S2. MDA-MB-231 mice that underwent fluorescence, bioluminescence, hyperpolarized MR and PET-CT imaging and reasons for their exclusion. Table S3. Antibodies used for Western blotting. Table S4. Expression of the transporters and enzymes and the activities of the enzymes involved in [18F]FDG and [1-13C]pyruvate uptake and metabolism in Colo205 tumors.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alice Denton.