14 results on '"de Gruijl, Tanja D."'
Search Results
2. Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types
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van den Ende, Tom, van den Boorn, Héctor G., Hoonhout, Nadine M., van Etten-Jamaludin, Faridi S., Meijer, Sybren L., Derks, Sarah, de Gruijl, Tanja D., Bijlsma, Maarten F., van Oijen, Martijn G.H., and van Laarhoven, Hanneke W.M.
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- 2020
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3. Vaccination approach to anti-angiogenic treatment of cancer
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Wentink, Madelon Q., Huijbers, Elisabeth J.M., de Gruijl, Tanja D., Verheul, Henk M.W., Olsson, Anna-Karin, and Griffioen, Arjan W.
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- 2015
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4. Mechanisms of intimate and long-distance cross-talk between glioma and myeloid cells: How to break a vicious cycle
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Wurdinger, Thomas, Deumelandt, Katrin, van der Vliet, Hans J., Wesseling, Pieter, and de Gruijl, Tanja D.
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- 2014
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5. Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival.
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Timmer, Florentine E.F., Geboers, Bart, Scheffer, Hester J., Bakker, Joyce, Ruarus, Alette H., Dijkstra, Madelon, van der Lei, Susan, Boon, Rianne, Nieuwenhuizen, Sanne, van den Bemd, Bente A.T., Schouten, Evelien A.C., van den Tol, Petrousjka M., Puijk, Robbert S., de Vries, Jan J.J., de Gruijl, Tanja D., and Meijerink, Martijn R.
- Abstract
To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC). Data on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR 10p) and during the total procedure (ΔR total) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets. A total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P <.001; R
2 = 0.91). A large change in tissue resistance significantly correlated with a better OS (P =.026) and longer time to disease progression (P =.045). Furthermore, a large change in tissue resistance was associated with CD8+ T cell activation through significant upregulation of Ki-67+ (P =.02) and PD-1+ (P =.047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P =.027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P =.039). IRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8+ T cell and cDC1 activation. [Display omitted] [ABSTRACT FROM AUTHOR]- Published
- 2023
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6. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix.
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Heeren, A Marijne, Punt, Simone, Bleeker, Maaike CG, Gaarenstroom, Katja N, van der Velden, Jacobus, Kenter, Gemma G, de Gruijl, Tanja D, and Jordanova, Ekaterina S
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- 2016
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7. Tumor-educated Tregs drive organ-specific metastasis in breast cancer by impairing NK cells in the lymph node niche.
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Kos, Kevin, Aslam, Muhammad A., van de Ven, Rieneke, Wellenstein, Max D., Pieters, Wietske, van Weverwijk, Antoinette, Duits, Danique E.M., van Pul, Kim, Hau, Cheei-Sing, Vrijland, Kim, Kaldenbach, Daphne, Raeven, Elisabeth A.M., Quezada, Sergio A., Beyaert, Rudi, Jacobs, Heinz, de Gruijl, Tanja D., and de Visser, Karin E.
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Breast cancer is accompanied by systemic immunosuppression, which facilitates metastasis formation, but how this shapes organotropism of metastasis is poorly understood. Here, we investigate the impact of mammary tumorigenesis on regulatory T cells (T regs) in distant organs and how this affects multi-organ metastatic disease. Using a preclinical mouse mammary tumor model that recapitulates human metastatic breast cancer, we observe systemic accumulation of activated, highly immunosuppressive T regs during primary tumor growth. Tumor-educated T regs show tissue-specific transcriptional rewiring in response to mammary tumorigenesis. This has functional consequences for organotropism of metastasis, as T reg depletion reduces metastasis to tumor-draining lymph nodes, but not to lungs. Mechanistically, we find that T regs control natural killer (NK) cell activation in lymph nodes, thereby facilitating lymph node metastasis. In line, an increased T reg /NK cell ratio is observed in sentinel lymph nodes of breast cancer patients compared with healthy controls. This study highlights that immune regulation of metastatic disease is highly organ dependent. [Display omitted] • Mammary tumorigenesis drives systemic expansion of highly immunosuppressive T regs • Tumor-educated T regs promote lymph node (LN) metastasis but not lung metastasis • T regs promote LN metastasis by local suppression of NK cells in the LN niche • LNs of breast cancer patients have elevated T reg and reduced NK cell accumulation Kos et al. demonstrate that breast cancer development is accompanied by systemic expansion of immunosuppressive regulatory T cells. The phenotype and function of tumor-educated T regs are uniquely shaped by the local tissue environment. Consequently, tumor-educated T regs impair local NK cell activity to enhance metastasis to lymph nodes, but not lungs. [ABSTRACT FROM AUTHOR]
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- 2022
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8. The role of transforming growth factor β in upper gastrointestinal cancers: A systematic review.
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Veen, Linde M., Skrabanja, Tim L.P., Derks, Sarah, de Gruijl, Tanja D., Bijlsma, Maarten F., and van Laarhoven, Hanneke W.M.
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Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Chemically engineered glycan-modified cancer vaccines to mobilize skin dendritic cells.
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Duinkerken, Sanne, Li, R. Eveline, van Haften, Floortje J., de Gruijl, Tanja D., Chiodo, Fabrizio, Schetters, Sjoerd T.T., and van Kooyk, Yvette
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CANCER vaccines , *DENDRITIC cells , *T cells , *SKIN , *VACCINES - Abstract
Dendritic cell (DC)–targeting vaccines show great promise in increasing antitumor immunity. Glycan-engineered vaccines facilitate both DC targeting and increased uptake by DCs for processing and presentation to CD4+ and CD8+ T cells to induce tumor-specific T-cell responses. However, the complexity of various DC subsets in skin tissues, expressing different glycan-binding receptors that can mediate vaccine uptake or drainage of vaccines via lymphatics directly to the lymph node–resident DCs, complicates the success of vaccines. Moreover, the influx of inflammatory immune cells to the site of vaccination, such as monocytes that differentiate to DCs and coexpress glycan-binding receptors, may contribute to the strength of DC-targeting glycovaccines for future clinical use. [ABSTRACT FROM AUTHOR]
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- 2019
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10. A safety and immunogenicity study of immunization with hVEGF26-104/RFASE in cynomolgus monkeys.
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Wentink, Madelon Q., Verheul, Henk M.W., Griffioen, Arjan W., Schafer, Kenneth A., McPherson, Susan, Early, Richard J., van der Vliet, Hans J., and de Gruijl, Tanja D.
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VASCULAR endothelial growth factors , *NEOVASCULARIZATION inhibitors , *CANCER , *ANTIGENS , *IMMUNOGENETICS , *KRA - Abstract
Introduction Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF 165 . hVEGF 26-104 /RFASE is based on the truncated protein hVEGF 26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant. Here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomolgus monkeys. Methods In total 54 cynomolgus monkeys were used and divided in 7 groups. Groups 1–3 were control groups, either receiving PBS alone (group 1), RFASE alone (group 2) or hVEGF 26-104 alone (group 3). Animals allocated to groups 4–7 received hVEGF 26-104 together with RFASE, but with varying doses of the antigen or the adjuvant. All animals were immunized four times with 2-week intervals and safety and immunogenicity were monitored until 3 days after the final immunization. Results Immunization induced an RFASE adjuvant dependent acute phase response. High titers of antibodies against hVEGF 26-104 and cross-reactive with hVEGF 165 , were found in monkey sera, 28 days after primer immunization. These antibodies were able to inhibit the binding of the monoclonal antibody bevacizumab with hVEGF 165 in a competition ELISA. Moreover, the biological activity of hVEGF 165 could be inhibited by the addition of immunized monkey serum in a VEGF specific bioassay. Importantly, no adverse events commonly observed with VEGF neutralization were observed throughout the study. Conclusion These data show that hVEGF 26-104 /RFASE can be safely administered in cynomolgus monkeys, induces the desired immune response and therefore support the clinical development of this vaccine. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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11. The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer.
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Schneiders, Famke L., Huijts, Charlotte M., Reijm, Martine, Bontkes, Hetty J., Verheul, Henk M.W., de Gruijl, Tanja D., and van der Vliet, Hans J.
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T cells , *CANCER patients , *ACUTE phase reaction , *TUMOR necrosis factors , *CYTOKINES - Abstract
Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro . We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Immune-competent human skin disease models.
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Bergers, Lambert I.J.C., Reijnders, Christianne M.A., van den Broek, Lenie J., Spiekstra, Sander W., de Gruijl, Tanja D., Weijers, Ester M., and Gibbs, Susan
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DRUG development , *DRUG use testing , *PLURIPOTENT stem cells , *AUTOIMMUNE diseases , *SKIN diseases , *PSORIASIS - Abstract
All skin diseases have an underlying immune component. Owing to differences in animal and human immunology, the majority of drugs fail in the preclinical or clinical testing phases. Therefore animal alternative methods that incorporate human immunology into in vitro skin disease models are required to move the field forward. This review summarizes the progress, using examples from fibrosis, autoimmune diseases, psoriasis, cancer and contact allergy. The emphasis is on co-cultures and 3D organotypic models. Our conclusion is that current models are inadequate and future developments with immune-competent skin-on-chip models based on induced pluripotent stem cells could provide a next generation of skin models for drug discovery and testing. [ABSTRACT FROM AUTHOR]
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- 2016
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13. In situ Delivery of Antigen to DC-SIGN+CD14+ Dermal Dendritic Cells Results in Enhanced CD8+ T-Cell Responses.
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Fehres, Cynthia M, van Beelen, Astrid J, Bruijns, Sven C M, Ambrosini, Martino, Kalay, Hakan, Bloois, Louis van, Unger, Wendy W J, Garcia-Vallejo, Juan J, Storm, Gert, de Gruijl, Tanja D, and Kooyk, Yvette van
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DENDRITIC cells , *MACROPHAGES , *T cells , *INTRADERMAL injections , *LIPOSOMES - Abstract
CD14+ dendritic cells (DCs) present in the dermis of human skin represent a large subset of dermal DCs (dDCs) that are considered macrophage-like cells with poor antigen (cross)-presenting capacity and limited migratory potential to the lymph nodes. CD14+ dDC highly express DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), a receptor containing potent endocytic capacity, facilitating intracellular routing of antigens to major histocompatibility complex I and II (MHC-I andII) loading compartments for the presentation to antigen-specific CD8+ and CD4+ T cells. Here we show using a human skin explant model that the in situ targeting of antigens to DC-SIGN using glycan-modified liposomes enhances the antigen-presenting capacity of CD14+ dDCs. Intradermal vaccination of liposomes modified with the DC-SIGN-targeting glycan LewisX, containing melanoma antigens (MART-1 or Gp100), accumulated in CD14+ dDCs and resulted in enhanced Gp100- or MART-1-specific CD8+ T-cell responses. Simultaneous intradermal injection of the cytokines GM-CSF and IL-4 as adjuvant enhanced the migration of the skin DCs and increased the expression of DC-SIGN on the CD14+ and CD1a+ dDCs. These data demonstrate that human CD14+ dDCs exhibit potent cross-presenting capacity when targeted in situ through DC-SIGN. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Bispecific antibody platforms for cancer immunotherapy.
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Lameris, Roeland, de Bruin, Renée C.G., Schneiders, Famke L., van Bergen en Henegouwen, Paul M.P., Verheul, Henk M.W., de Gruijl, Tanja D., and van der Vliet, Hans J.
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CANCER treatment , *IMMUNOTHERAPY , *BIOENGINEERING , *TUMOR immunology , *ANTINEOPLASTIC agents , *BISPECIFIC antibodies - Abstract
Over the past decades advances in bioengineering and expanded insight in tumor immunology have resulted in the emergence of novel bispecific antibody (bsAb) constructs that are capable of redirecting immune effector cells to the tumor microenvironment. (Pre-) clinical studies of various bsAb constructs have shown impressive results in terms of immune effector cell retargeting, target dependent activation and the induction of anti-tumor responses. This review summarizes recent advances in the field of bsAb-therapy and limitations that were encountered. Furthermore, we will discuss potential future developments that can be expected to take the bsAb approach successfully forward. [ABSTRACT FROM AUTHOR]
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- 2014
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