24 results on '"de Gruijl, Tanja D."'
Search Results
2. Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer
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Toffoli, Elisa C, primary, van Vliet, Amanda A, additional, Verheul, Henk W M, additional, van der Vliet, Hans J, additional, Tuynman, Jurriaan, additional, Spanholtz, Jan, additional, and de Gruijl, Tanja D, additional
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- 2023
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3. Selectively hampered activation of lymph node-resident dendritic cells precedes profound T cell suppression and metastatic spread in the breast cancer sentinel lymph node
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van Pul, Kim M., Vuylsteke, Ronald J.C.L.M., van de Ven, Rieneke, te Velde, Elisabeth A., Rutgers, Emiel J. Th., van den Tol, Petrousjka M., Stockmann, Hein B.A.C., and de Gruijl, Tanja D.
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- 2019
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4. Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth
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Heeren, Anne Marijne, primary, Rotman, Jossie, additional, Samuels, Sanne, additional, Zijlmans, Henry J M A A, additional, Fons, Guus, additional, van de Vijver, Koen K, additional, Bleeker, Maaike C G, additional, Kenter, Gemma G, additional, Jordanova, Ekaterina J, additional, and de Gruijl, Tanja D, additional
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- 2021
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5. HPV-16 E6/E7 DNA tattoo vaccination using genetically optimized vaccines elicit clinical and immunological responses in patients with usual vulvar intraepithelial neoplasia (uVIN): a phase I/II clinical trial
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Bakker, Noor Alida Maria, primary, Rotman, Jossie, additional, van Beurden, Marc, additional, Zijlmans, Henry J MAA, additional, van Ruiten, Maartje, additional, Samuels, Sanne, additional, Nuijen, Bastiaan, additional, Beijnen, Jos, additional, De Visser, Karin, additional, Haanen, John, additional, Schumacher, Ton, additional, de Gruijl, Tanja D, additional, Jordanova, Ekaterina S, additional, Kenter, Gemma G, additional, van den Berg, Joost H, additional, and van Trommel, Nienke E, additional
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- 2021
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6. T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A+CD141+ cDC1 and CD14+ antigen-presenting cell recruitment
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Koster, Bas D, primary, López González, Marta, additional, van den Hout, Mari FCM, additional, Turksma, Annelies W, additional, Sluijter, Berbel JR, additional, Molenkamp, Barbara G, additional, van Leeuwen, Paul AM, additional, Vosslamber, Saskia, additional, Scheper, Rik J, additional, van den Eertwegh, Alfons JM, additional, van den Tol, M Petrousjka, additional, Jordanova, Ekaterina J, additional, and de Gruijl, Tanja D, additional
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- 2021
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7. Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy
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Prokopi, Anastasia, primary, Tripp, Christoph H, additional, Tummers, Bart, additional, Hornsteiner, Florian, additional, Spoeck, Sarah, additional, Crawford, Jeremy Chase, additional, Clements, Derek R, additional, Efremova, Mirjana, additional, Hutter, Katharina, additional, Bellmann, Lydia, additional, Cappellano, Giuseppe, additional, Cadilha, Bruno L, additional, Kobold, Sebastian, additional, Boon, Louis, additional, Ortner, Daniela, additional, Trajanoski, Zlatko, additional, Chen, Suzie, additional, de Gruijl, Tanja D, additional, Idoyaga, Juliana, additional, Green, Douglas R, additional, and Stoitzner, Patrizia, additional
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- 2021
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8. Breast cancer-induced immune suppression in the sentinel lymph node is effectively countered by CpG-B in conjunction with inhibition of the JAK2/STAT3 pathway
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van Pul, Kim M, primary, Vuylsteke, Ronald J C L M, additional, de Beijer, Monique T A, additional, van de Ven, Rieneke, additional, van den Tol, M Petrousjka, additional, Stockmann, Hein B A C, additional, and de Gruijl, Tanja D, additional
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- 2020
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9. Insights from immuno-oncology: the Society for Immunotherapy of Cancer Statement on access to IL-6-targeting therapies for COVID-19
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Ascierto, Paolo Antonio, primary, Fox, Bernard A, additional, Urba, Walter J, additional, Anderson, Ana Carrizosa, additional, Atkins, Michael B, additional, Borden, Ernest C, additional, Brahmer, Julie R, additional, Butterfield, Lisa H, additional, Cesano, Alessandra, additional, Chen, Daniel S, additional, de Gruijl, Tanja D, additional, Dillman, Robert O, additional, Drake, Charles G, additional, Emens, Leisha A, additional, Gajewski, Thomas F, additional, Gulley, James L, additional, Stephen Hodi Jr, F, additional, Hwu, Patrick, additional, Kaufman, David, additional, Kaufman, Howard L, additional, Lotze, Michael T, additional, McNeel, Douglas G, additional, Margolin, Kim A, additional, Marincola, Francesco M, additional, Mastrangelo, Michael J, additional, Maus, Marcela V, additional, Parkinson, David R, additional, Romero, Pedro J, additional, Sondel, Paul M, additional, Spranger, Stefani, additional, Sznol, Mario, additional, Weiner, George J, additional, Wigginton, Jon M, additional, and Weber, Jeffrey S, additional
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- 2020
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10. Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases
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Ferns, Debbie M., primary, Heeren, A. Marijne, additional, Samuels, Sanne, additional, Bleeker, Maaike C. G., additional, de Gruijl, Tanja D., additional, Kenter, Gemma G., additional, and Jordanova, Ekaterina S., additional
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- 2016
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11. Adjuvant treatment of early-stage melanoma by local i.d. administration of low-dose CpG-B and GM-CSF increases recurrence-free survival: long-term follow-up of three randomized clinical trials
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de Gruijl, Tanja D, primary, Koster, Bas D, additional, van den Hout, Mari FCM, additional, Sluijter, Berbel JR, additional, Molenkamp, Barbara G, additional, Vuylsteke, Ronald JCLM, additional, van Leeuwen, Paul AM, additional, Scheper, Rik J, additional, van den Tol, Petrousjka, additional, and van den Eertwegh, Alfons, additional
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- 2015
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12. Counteracting breast-cancer induced immune suppression by reactivating lymph node-resident conventional dendritic cells (LNR-cDC)
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van de Ven, Rieneke, primary, van Pul, Kim, additional, Aliabadi, Shaghayegh, additional, van den Tol, Petrousjka, additional, te Velde, Lisette A, additional, Rutgers, Emiel JTh, additional, Vuylsteke, Ronald JCLM, additional, Stockmann, Hein BAC, additional, Dubay, Christopher, additional, Harrington, Chris, additional, Fox, Bernard A, additional, and de Gruijl, Tanja D, additional
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- 2015
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13. Profiling of suppressive immune subsets in metastasis negative and positive sentinel lymph nodes from patients with HER2- breast cancer
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van de Ven, Rieneke, primary, van Pul, Kim, additional, Aliabadi, Shaghayegh, additional, van den Tol, M Petrousjka, additional, Haley, Daniel, additional, Tamakawa, Raina, additional, Vuylsteke, Ronald J, additional, Stockmann, Hein B, additional, Cramer, Julie L, additional, Urba, Walter J, additional, Fox, Bernard A, additional, and de Gruijl, Tanja D, additional
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- 2014
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14. Specific tumor targeting and activation of Vγ9Vδ2 T cells by bi-specific nanobodies
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Stam, Anita, primary, de Bruin, Renée, additional, Roovers, Rob, additional, van Bergen en Henegouwen, Paul, additional, Verheul, Henk, additional, de Gruijl, Tanja D, additional, and van der Vliet, Hans, additional
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- 2014
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15. Evidence for a coordinate role of CD14+ antigen-presenting cells and regulatory T cells in conditioning the microenvironment of metastatic lymph nodes from patients with cervical cancer
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Heeren, Marijne, primary, Koster, Bas, additional, Samuels, Sanne, additional, Ferns, Debbie, additional, Chondronasiou, Dafni, additional, Kenter, Gemma, additional, Jordanova, Ekaterina S, additional, and de Gruijl, Tanja D, additional
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- 2014
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16. Myeloid derived suppressor and dendritic cell subsets are related to clinical outcome in prostate cancer patients treated with prostate GVAX and ipilimumab
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Santegoets, Saskia JAM, primary, Stam, Anita GM, additional, Lougheed, Sinéad M, additional, Gall, Helen, additional, Jooss, Karin, additional, Sacks, Natalie, additional, Hege, Kristen, additional, Lowy, Israel, additional, Scheper, Rik J, additional, Gerritsen, Winald R, additional, van den Eertwegh, Alfons JM, additional, and de Gruijl, Tanja D, additional
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- 2014
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17. Pre-operative intradermal administration of CpG-B ± GM-CSF in stage I-III melanoma patients arms the sentinel lymph node: evidence for reduced tumor spread
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van den Hout, Mari F, primary, Koster, Bas D, additional, Scheper, Rik J, additional, van de Ven, Rieneke, additional, Sluijter, Berbel J, additional, Molenkamp, Barbara G, additional, van den Eertwegh, Alfons J, additional, van Leeuwen, Paul A, additional, van den Tol, Petrousjka M, additional, and de Gruijl, Tanja D, additional
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- 2013
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18. Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy
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Prokopi, Anastasia, Tripp, Christoph H, Tummers, Bart, Hornsteiner, Florian, Spoeck, Sarah, Crawford, Jeremy Chase, Clements, Derek R, Efremova, Mirjana, Hutter, Katharina, Bellmann, Lydia, Cappellano, Giuseppe, Cadilha, Bruno L, Kobold, Sebastian, Boon, Louis, Ortner, Daniela, Trajanoski, Zlatko, Chen, Suzie, de Gruijl, Tanja D, Idoyaga, Juliana, Green, Douglas R, Stoitzner, Patrizia, Medical oncology laboratory, AII - Cancer immunology, and CCA - Cancer biology and immunology
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Immune Cell Therapies and Immune Cell Engineering ,Sequence Analysis, RNA ,Programmed Cell Death 1 Receptor ,Melanoma, Experimental ,Dendritic Cells ,immunomodulation ,Antibodies ,Coculture Techniques ,Gene Expression Regulation, Neoplastic ,Mice ,Poly I-C ,Cell Line, Tumor ,melanoma ,tumor microenvironment ,Animals ,Humans ,immunotherapy ,CD40 Antigens ,Hepatitis A Virus Cellular Receptor 2 ,Immune Checkpoint Inhibitors ,Neoplasm Staging ,Skin - Abstract
Background Immunotherapy with checkpoint inhibitors has shown impressive results in patients with melanoma, but still many do not benefit from this line of treatment. A lack of tumor-infiltrating T cells is a common reason for therapy failure but also a loss of intratumoral dendritic cells (DCs) has been described. Methods We used the transgenic tg(Grm1)EPv melanoma mouse strain that develops spontaneous, slow-growing tumors to perform immunological analysis during tumor progression. With flow cytometry, the frequencies of DCs and T cells at different tumor stages and the expression of the inhibitory molecules programmed cell death protein-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells were analyzed. This was complemented with RNA-sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR) analysis to investigate the immune status of the tumors. To boost DC numbers and function, we administered Fms-related tyrosine 3 ligand (Flt3L) plus an adjuvant mix of polyI:C and anti-CD40. To enhance T cell function, we tested several checkpoint blockade antibodies. Immunological alterations were characterized in tumor and tumor-draining lymph nodes (LNs) by flow cytometry, CyTOF, microarray and RT-qPCR to understand how immune cells can control tumor growth. The specific role of migratory skin DCs was investigated by coculture of sorted DC subsets with melanoma-specific CD8+ T cells. Results Our study revealed that tumor progression is characterized by upregulation of checkpoint molecules and a gradual loss of the dermal conventional DC (cDC) 2 subset. Monotherapy with checkpoint blockade could not restore antitumor immunity, whereas boosting DC numbers and activation increased tumor immunogenicity. This was reflected by higher numbers of activated cDC1 and cDC2 as well as CD4+ and CD8+ T cells in treated tumors. At the same time, the DC boost approach reinforced migratory dermal DC subsets to prime gp100-specific CD8+ T cells in tumor-draining LNs that expressed PD-1/TIM-3 and produced interferon γ(IFN 3)/tumor necrosis factor α (TNFα). As a consequence, the combination of the DC boost with antibodies against PD-1 and TIM-3 released the brake from T cells, leading to improved function within the tumors and delayed tumor growth. Conclusions Our results set forth the importance of skin DC in cancer immunotherapy, and demonstrates that restoring DC function is key to enhancing tumor immunogenicity and subsequently responsiveness to checkpoint blockade therapy.
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19. Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer.
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Wondergem NE, Miedema IHC, van de Ven R, Zwezerijnen GJC, de Graaf P, Karagozoglu KH, Hendrickx JJ, Eerenstein SEJ, Bun RJ, Mulder DC, Voortman J, Boellaard R, Windhorst AD, Hagers JP, Peferoen LAN, de Gruijl TD, Bloemena E, Brakenhoff RH, Leemans CR, and Menke-van der Houven van Oordt CW
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- Humans, Male, Female, Middle Aged, Aged, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Molecular Imaging methods, Nivolumab therapeutic use, Nivolumab pharmacology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Programmed Cell Death 1 Receptor antagonists & inhibitors, Positron-Emission Tomography methods, Adult, Mouth Neoplasms drug therapy, Mouth Neoplasms diagnostic imaging, Mouth Neoplasms pathology, Neoadjuvant Therapy methods
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Background: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome., Methods: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included
18 F-BMS-986192 (PD-L1) PET and18 F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology., Results: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1., Conclusion: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations., Competing Interests: Competing interests: RvdV has received research funding from Genmab BV. TDdG is scientific advisor to Immunicum, GE Health, and Lava Therapeutics, holds stock from LAVA Therapeutics and received research funding from Idera Pharmaceuticals (now Aceragen). RHB received research grants from KWF Kankerbestrijding/Dutch Cancer Society, Cancer Center Amsterdam Foundation, ZonMW and NWO, Genmab BV and the Hanarth Foundation and is on the advisory board of Nanobiotix. He has a scientific collaboration with Orfenix BV and Qialix DoT. CRL received research grants from KWF Kankerbestrijding/Dutch Cancer Society, Cancer Center Amsterdam Foudation, Genmab BV, BMS and the Hanarth Foundation and is on the advisory board of Merck & Co. CWM-vdHvO received research grants from BMS, Boeringher Ingelheim, GSK, Pfizer and AstraZeneca and consulted for GE Health Care, Novartis and EliLilly. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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20. Mapping the complexity and diversity of tertiary lymphoid structures in primary and peritoneal metastatic gastric cancer.
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Groen-van Schooten TS, Franco Fernandez R, van Grieken NCT, Bos EN, Seidel J, Saris J, Martínez-Ciarpaglini C, Fleitas TC, Thommen DS, de Gruijl TD, Grootjans J, and Derks S
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- Humans, Male, Female, Tumor Microenvironment, Stomach Neoplasms pathology, Stomach Neoplasms immunology, Tertiary Lymphoid Structures immunology, Peritoneal Neoplasms secondary, Peritoneal Neoplasms immunology
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Background: Tertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment., Methods: Spatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45
+ immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases., Results: We identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer., Conclusion: The observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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21. Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by 18 F-BMS986-192 PET: pooled analysis of data from four solid tumor types.
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Miedema IHC, Pouw JEE, Kwakman A, Zwezerijnen GJC, Huisman MC, Timmer FEF, van de Ven R, de Gruijl TD, Hospers GAP, de Langen AJ, and Menke-van der Houven van Oordt CW
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- Humans, Male, Female, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms diagnostic imaging, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Middle Aged, Aged, B7-H1 Antigen metabolism, Lymph Nodes metabolism, Lymph Nodes pathology, Lymph Nodes diagnostic imaging, Positron-Emission Tomography methods
- Abstract
Introduction: Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using
18 F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events., Methods: Four18 F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV)mean , lymph node SUVmax ) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted., Results: Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUVmean 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUVmax 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUVmax 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity., Conclusion: PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer., Competing Interests: Competing interests: RvdV: Research funding for Institute: Genmab B.V. TDdG: Research funding for Institute: Idera Pharmaceuticals (now Aceragen); Consultancy: GE Health, LAVA Therapeutics, Mendus (all to Institute); holds stocks from LAVA Therapeutics. GAPH: Research funding for Institute: Bristol-Myers Squibb, Seerave. Consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, Pierre Fabre. AJdL: Research funding for Institute: Bristol-Myers Squibb, MSD, Boehringer Ingelheim, AstraZeneca. Non-financial support from Merck Serono, non-financial support from Roche. CWM-vdHvO: Research funding for Institute: Bristol-Myers Squibb, Boehringer Ingelheim, GSK, Pfizer; AstraZeneca. Consultancy: GE Health Care, Novartis, Eli Lilly. IHCM, JEEP, AK, GJCZ, MCH, FEFT: No competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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22. Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.
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Luke JJ, Davar D, Andtbacka RH, Bhardwaj N, Brody JD, Chesney J, Coffin R, de Baere T, de Gruijl TD, Fury M, Goldmacher G, Harrington KJ, Kaufman H, Kelly CM, Khilnani AD, Liu K, Loi S, Long GV, Melero I, Middleton M, Neyns B, Pinato DJ, Sheth RA, Solomon SB, Szapary P, and Marabelle A
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- Humans, Immunotherapy methods, Societies, Medical, Tumor Microenvironment, Neoplasms therapy, Neoplasms, Second Primary
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Background: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis., Methods: An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript., Results: The panel determined unique clinical trial designs tailored to different stages of cancer development-from premalignant to unresectable/metastatic-that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments., Conclusions: The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most., Competing Interests: Competing interests: JJL: Researcher: AbbVie, Astellas, Astrazeneca, Bristol-Myers Squibb, Corvus, Day 1, EMD Serono, Fstar, Genmab, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, XencorConsultant/Advisor/Speaker: Abbvie, Agenus, Alnylam, Atomwise, Bayer, Bristol-Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, Macrogenics, Merck, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Replimmune, Ribon, Roivant, Servier, STINGthera, Synlogic, Synthekine, 7 Hills, Affivant, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio (stock) Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, physIQ, Pyxis, Saros, STipe, Tempest, Abbvie, Agenus, Amgen, Immutep, Evaxion. DD: Grants/Research Support (institutional): Arcus, Immunocore, Merck, Regeneron Pharmaceuticals, Tesaro/GSK. Consultant: ACM Bio, Ascendis, Castle, Clinical Care Options (CCO), Gerson Lehrman Group (GLG), Immunitas, Medical Learning Group (MLG), Replimmune, Trisalus, Xilio Therapeutics. CE Speakers’ Bureau: Castle Biosciences. Stockholder: None. Intellectual Property: US Patent 63/124,231, "Compositions and Methods for Treating Cancer", December 11, 2020 US Patent 63/208,719, "Compositions and Methods For Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer", June 9, 2021. AM: Owner: HiFiBio, Deka Bio, Hotspot Therapeutics, Shattuck Labs, Researcher: Astra Zeneca, BMS, Sanofi, Consultant/Advisor/Speaker: Gritstone, Innate Pharma, Neogene, Deka Bio, Hotspot therapeutics, J&J, Medicxi, Depth Charge, BiolineRx, Clover Pharma, Grey Wolf, Lytix, RedX, HiFiBio, ImCheck, Applied Materials, Takeda, Shattuck Labs, Marengo therapeutics, Pierre Fabre, Third Rock Ventures, SotioPublicly Traded Stocks: Centessa. RHA–Employee: Seven & Eight Biopharmaceuticals. Ownership Interest Less Than 5 Percent: Seven & Eight Biopharmaceuticals. NB: Consulting Fees: Novartis, Apricity, Rome Therapeutics, BreakBio, Carisma Therapeutics, CureVac, BioNTech, Gilead, Tempest Therapeutics, Boehringer Ingelheim, Contracted Research: Regeneron Pharmaceutics, Dragonfly Therapeutics, Harbour Biomed Sciences, Ownership Interest Less Than 5 Percent: BreakBio, Apricity. JDB: Researcher: Merck, Genentech, Astrazeneca, Kite/Gilead, BMS, Celldex, Oncovir, Seattle Genetics, ADC Therapeutics, Epizyme, Consultant/Advisor/Speaker: Merck, Genentech, Astrazeneca, Kite/Gilead, BMS, Seattle Genetics, ADC Therapeutics, Epizyme, Asgaard Therapeutics, Global BioAccess, SIRPant Immunotherapeutics. JC: Executive Role: UofL Health, Researcher: Amgen, Iovance, Fate, Replimune, Consultant/Advisor/Speaker: Replimune advisory board 2020-21, Royalties or Patent Beneficiary: US Patents: University of Louisville. RC: Employee: Replimune. TdB: Consultant/Advisor/Speaker: Terumo, Boston Scientific, Astra Zeneca, Nanobiotix, Quantum Surgical, Guerbet, Cook medical, Johnson & Johnson. TDdG: Patents: (1) The use of cytostatics for the accelerated differentiation of DC; WO2009019320-A2; WO2009019320-A3; AU2008285598-A1; EP2281030-A2; CA2724018-A1; US2011117051-A1. US8,470,789B2; DCprime BV. (2) Immunoglobulins binding human Vγ9VÎ’2 T cell receptors; P31885NL00. Consulting Fees: Mendus (formerly Immunicum, formerly DCPrime BV), Partner Therapeutics, GE Health, LAVA Therapeutics, Contracted Research: Idera Pharmaceuticals, Macrophage Parma, Ownership Interest Less Than 5 Percent: LAVA Therapeutics. MGF: Employee: Regeneron. GVG: Employee: Merck. Publicly Traded Stocks: Immunogen, Aveo, Beta Bionics. KJH: Researcher: AstraZeneca, Boehringer-Ingelheim, Replimune, Consultant/Advisor/Speaker: Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak, Eisai, Inzen, Merck-Serono, MSD, Oncolys, Pfizer, Replimune. HK: Employee: Ankyra Therapeutics. Consultant/Advisor/Speaker: Castle Biosciences, Marengo Therapeutics. CMK: Researcher: Amgen, Merck & Co., Kartos Pharmaceuticals, EMD Serono, Deciphera Pharmaceuticals, Eily lilly, Blueprint Medicines, Incyte Corporation, Clovis Oncology, BMS, Aadi Bioscience, Pfizer, Iterion Therapeutics, Springworks Therapeutics, Nektar Therapeutics, GSK, Adaptimmune, Medimmune, Bioatla, Oncternal Therapeutics, Daiichi- Sankyo Co. Traycon Pharm, Eisai. Ascentage Pharma, Hutchison Medipharma, Salarius Pharmaceuticals, Loxo Oncology, -BTG Specialty Pharmaceuticals, AStex Pharmaceuticals, Xencor, bayer healthcare, Athenex pharmaceuticals, servier, K- group Beta, Trilliium Pharmaceuticals, Ayala Pharmaceuticals, Ningbo Newbay Technology Development, Rain Therapeutics, Inhibrx, C4 Therapeutics, Foghorn Therapeutics, Theseus Pharmaceuticals, Cogent Therapeutics, Curadev PharmaRegeneron, Consultant/Advisor/Speaker: Chemocentryx, Kartos, Servier, Immunicom, Other: Spouse employed by Daichii Sankyo with stock options. ADK: Employee: Merck. KL: Employee: Marengo Therapeutics. SL: Executive Role: Big Against Cancer (Belgium), Breast Cancer Trials (Australia), International Breast Cancer Study Group (Switzerland) Researcher: Research funding to institution from Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, Astra Zeneca, Roche-Genentech and Seattle Genetics, Consultant/Advisor/Speaker: Consultant (not compensated) to Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Eli Lilly, Pfizer, Gilead Therapeutics and Roche-Genentech. Consultant (paid to institution) to Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Astra Zeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly and Bristol Meyers Squibb, Role: Presenter (Speaker). GVL: Consultant/Advisor/Speaker: Consultant Advisor for Agenus, Amgen, Array Biopharma, AstraZeneca UK, Boehringer Ingelheim International, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme (Australia), Merck Sharpe & Dohme, Novartis Pharma AG, PHMR, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals. IM: Consulting Fees: Bristol-Myers Squibb, F-STAR, Alligator, Pharma Mar, AstraZeneca, Numab Therapeutics, Roche, Amunix, Gossamer, Molecular Partners, Merck-Serono, Genmab, PharmaMar, Contracted Research: Roche, Bristol-Myers Squibb, Highlight Therapeutics, Alligator, Genmab, Astrazeneca. MRM: Researcher : Roche, Astrazeneca, Novartis, Immunocore, BMS, Pfizer, Merck/MSD, Regeneron, BiolineRx, Replimune, GRAIL, Alkermes, iOx, Vaccitech, Consultant/Advisor/Speaker: Infinitopes. BN: Researcher: As a principal investigator for clinical trials sponsored by UZ Brussel, my institution received support from Novartis, Pfizer, Bayer, BMS, MSD, Pierre-Fabre, Amgen, Consultant/Advisor/Speaker: Novartis, BMS, MSD, Pfizer, Pierre-Fabre, Amgen. DJP: Consulting Fees: ViiV Healthcare, Bayer, Hoffman La Roche, EISAI, H3B, MiNa Alpha Therapeutics, DaVolterra, Fees for Non CE Services: Hoffmann La Roche, EISAI, Contracted Research: Merck Sharpe and Dohme, Bristol Myers Squibb (to institution). RAS: Researcher: Boston ScientificConsultant/Advisor/Speaker: Cook Medical, TriSalus, Replimune, Medtronic. SBS: Owner: Aperture Medical Technology, Executive Role: Aperture Medical Technology, Researcher: GE Healthcare, Johnson & Johnson, Elesta, Consultant/Advisor/Speaker: GE Healthcare, XACT Robotics, Microbot, Candel Therapeutics, Varian, Merck & Co., Royalty and Patent Beneficiary: Aperture Medical Technology, Publicly Traded Stocks: Johnson & Johnson, Poseidx Therapeutics, Motus GI, Sientra, Avadel, Lantheus. PS: Employee: Johnson & Johnson, Publicly Traded Stocks: Johnson & Johnson. SITC staff members SMW, CG, AK, NL, EG and KJ have no disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
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23. Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions.
- Author
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Lameris R, Shahine A, Veth M, Westerman B, Godfrey DI, Lutje Hulsik D, Brouwer P, Rossjohn J, de Gruijl TD, and van der Vliet HJ
- Subjects
- Humans, Phosphatidylserines metabolism, Annexin A5, T-Lymphocyte Subsets, Hepatitis A Virus Cellular Receptor 2 metabolism, Single-Domain Antibodies metabolism
- Abstract
Background: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach., Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d
+ tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography., Results: Anti-CD1d VHH1D17 strongly enhances annexin V binding to CD1d+ tumor cells but this does not reflect induction of apoptosis. Instead, we show that VHH1D17 enhances presentation of phosphatidylserine (PS) in CD1d and that this is saposin dependent. The crystal structure of the VHH1D17-CD1d(endogenous lipid) complex demonstrates that VHH1D17 binds the A'-pocket of CD1d, leaving the lipid headgroup solvent exposed, and has an electro-negatively charged patch which could be involved in the enhanced PS presentation by CD1d. Presentation of PS in CD1d does not trigger phagocytosis but leads to greatly enhanced binding of T-cell immunoglobulin and mucin domain containing molecules (TIM)-1 to TIM-3, TIM-4 and induces TIM-3 signaling., Conclusion: Our findings reveal the existence of an immune modulatory CD1d(PS)-TIM axis with potentially unexpected implications for immune regulation in both physiological and pathological conditions., Competing Interests: Competing interests: DLH, PB and HJvdV are employees of LAVA Therapeutics, a company that develops bispecific gamma-delta T-cell engagers, and own LAVA Therapeutics shares and/or stock options. RL, TDdG and HJvdV are named inventors on international patent application WO 2016/122320 Al (‘Single domain antibodies targeting CD1d’) which partially relates to the work described in this paper. TDdG is a consultant for and a shareholder of LAVA Therapeutics. RL and MV were funded by a LAVA Therapeutics grant to Amsterdam UMC. JR has received funding from LAVA Therapeutics. DIG is a member of the scientific advisory board and a shareholder of Avalia Immunotherapies, a company working on NKT cell-based vaccines and is an inventor on patent applications WO 2021/127745 and WO 2021/127744 that describe effects of cross-linking CD1 molecules and WO2020/231274 that describes CD1d-dependent glycopeptide vaccines., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
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24. T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A + CD141 + cDC1 and CD14 + antigen-presenting cell recruitment.
- Author
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Koster BD, López González M, van den Hout MF, Turksma AW, Sluijter BJ, Molenkamp BG, van Leeuwen PA, Vosslamber S, Scheper RJ, van den Eertwegh AJ, van den Tol MP, Jordanova EJ, and de Gruijl TD
- Subjects
- Adult, Aged, Cells, Cultured, Clinical Trials, Phase II as Topic, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Humans, Injections, Intradermal, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Male, Melanoma immunology, Melanoma metabolism, Middle Aged, Neoplasm Staging, Randomized Controlled Trials as Topic, Skin Neoplasms immunology, Skin Neoplasms metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism, Time Factors, Treatment Outcome, Tumor Microenvironment, Antineoplastic Agents administration & dosage, Dendritic Cells drug effects, Lectins, C-Type metabolism, Lipopolysaccharide Receptors metabolism, Lymphocytes, Tumor-Infiltrating drug effects, Melanoma drug therapy, Oligodeoxyribonucleotides administration & dosage, Receptors, Mitogen metabolism, Skin Neoplasms drug therapy, T-Lymphocytes drug effects, Thrombomodulin metabolism
- Abstract
Background: We previously reported CpG-B injection at the primary tumor excision site prior to re-excision and sentinel node biopsy to result in immune activation of the sentinel lymph node (SLN), increased melanoma-specific CD8
+ T cell rates in peripheral blood, and prolonged recurrence-free survival. Here, we assessed recruitment and activation of antigen-presenting cell (APC) subsets in the SLN and at the injection site in relation to T cell infiltration., Methods: Re-excision skin specimens from patients with clinical stage I-II melanoma, collected 7 days after intradermal injection of either saline (n=10) or 8 mg CpG-B (CPG7909, n=12), were examined by immunohistochemistry, quantifying immune subsets in the epidermis, papillary, and reticular dermis. Counts were related to flow cytometric data from matched SLN samples. Additional in vitro cultures and transcriptional analyses on peripheral blood mononuclear cells (PBMCs) were performed to ascertain CpG-induced APC activation and chemokine profiles., Results: Significant increases in CD83+ , CD14+ , CD68+ , and CD123+ APC were observed in the reticular dermis of CpG-B-injected skin samples. Fluorescent double/triple staining revealed recruitment of both CD123+ BDCA2+ plasmacytoid dendritic cells (DCs) and BDCA3/CD141+ CLEC9A+ type-1 conventional DC (cDC1), of which only the cDC1 showed considerable levels of CD83 expression. Simultaneous CpG-B-induced increases in T cell infiltration were strongly correlated with both cDC1 and CD14 counts. Moreover, cDC1 and CD14+ APC rates in the reticular dermis and matched SLN suspensions were positively correlated. Flow cytometric, transcriptional, and chemokine release analyses of PBMC, on in vitro or in vivo exposure to CpG-B, indicate a role for the activation and recruitment of both cDC1 and CD14+ monocyte-derived APCs in the release of CXCL10 and subsequent T cell infiltration., Conclusion: The CpG-B-induced concerted recruitment of cDC1 and CD14+ APC to the injection site and its draining lymph nodes may allow for both the (cross-)priming of T cells and their subsequent homing to effector sites., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2021
- Full Text
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