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45 results on '"Lougheed, Sinéad M."'

1. Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus

Author

Werter, Inge M., Huijts, Charlotte M., Lougheed, Sinéad. M., Hamberg, Paul, Polee, Marco B., Tascilar, Metin, Los, Maartje, Haanen, John B. A. G., Helgason, Helgi H., Verheul, Henk M., de Gruijl, Tanja D., van der Vliet, Hans J., and for the Dutch WIN-O Consortium

Published
2019
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4. Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition

Author

van den Ende, Tom, primary, Ezdoglian, Aiarpi, additional, Baas, Lisanne M., additional, Bakker, Joyce, additional, Lougheed, Sinéad M., additional, Harrasser, Micaela, additional, Waasdorp, Cynthia, additional, van Berge Henegouwen, Mark I., additional, Hulshof, Maarten C.C.M., additional, Haj Mohammad, Nadia, additional, van Hillegersberg, Richard, additional, Mook, Stella, additional, van der Laken, Conny J., additional, van Grieken, Nicole C.T., additional, Derks, Sarah, additional, Bijlsma, Maarten F., additional, van Laarhoven, Hanneke W.M., additional, and de Gruijl, Tanja D., additional

Published
2023
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6. Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition

Author

MS Medische Oncologie, Cancer, MS CGO, MS Radiotherapie, van den Ende, Tom, Ezdoglian, Aiarpi, Baas, Lisanne M, Bakker, Joyce, Lougheed, Sinéad M, Harrasser, Micaela, Waasdorp, Cynthia, van Berge Henegouwen, Mark I, Hulshof, Maarten C C M, Haj Mohammad, Nadia, van Hillegersberg, Richard, Mook, Stella, van der Laken, Conny J, van Grieken, Nicole C T, Derks, Sarah, Bijlsma, Maarten F, van Laarhoven, Hanneke W M, de Gruijl, Tanja D, MS Medische Oncologie, Cancer, MS CGO, MS Radiotherapie, van den Ende, Tom, Ezdoglian, Aiarpi, Baas, Lisanne M, Bakker, Joyce, Lougheed, Sinéad M, Harrasser, Micaela, Waasdorp, Cynthia, van Berge Henegouwen, Mark I, Hulshof, Maarten C C M, Haj Mohammad, Nadia, van Hillegersberg, Richard, Mook, Stella, van der Laken, Conny J, van Grieken, Nicole C T, Derks, Sarah, Bijlsma, Maarten F, van Laarhoven, Hanneke W M, and de Gruijl, Tanja D

Published
2023

8. Sensing of latent EBV infection through exosomal transfer of 5′pppRNA

Author

Baglio, S. Rubina, van Eijndhoven, Monique A. J., Koppers-Lalic, Danijela, Berenguer, Jordi, Lougheed, Sinéad M., Gibbs, Susan, Léveillé, Nicolas, Rinkel, Rico N. P. M., Hopmans, Erik S., Swaminathan, Sankar, Verkuijlen, Sandra A. W. M., Scheffer, George L., van Kuppeveld, Frank J. M., de Gruijl, Tanja D., Bultink, Irene E. M., Jordanova, Ekaterina S., Hackenberg, Michael, Piersma, Sander R., Knol, Jaco C., Voskuyl, Alexandre E., Wurdinger, Thomas, Jiménez, Connie R., Middeldorp, Jaap M., and Pegtel, D. Michiel

Published
2016

9. Local delivery of low-dose anti–CTLA-4 to the melanoma lymphatic basin leads to systemic T reg reduction and effector T cell activation

Author

van Pul, Kim M., primary, Notohardjo, Jessica C. L., additional, Fransen, Marieke F., additional, Koster, Bas D., additional, Stam, Anita G. M., additional, Chondronasiou, Dafni, additional, Lougheed, Sinéad M., additional, Bakker, Joyce, additional, Kandiah, Vinitha, additional, van den Tol, M. Petrousjka, additional, Jooss, Karin, additional, Vuylsteke, Ronald J. C. L. M., additional, van den Eertwegh, Alfons J. M., additional, and de Gruijl, Tanja D., additional

Published
2022
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10. T cell profiling reveals high CD4+CTLA-4+ T cell frequency as dominant predictor for survival after Prostate GVAX/ipilimumab treatment

Author

Santegoets, Saskia J. A. M., Stam, Anita G. M., Lougheed, Sinéad M., Gall, Helen, Scholten, Petra E. T., Reijm, Martine, Jooss, Karin, Sacks, Natalie, Hege, Kristen, Lowy, Israel, Cuillerot, Jean-Marie, von Blomberg, B. Mary E., Scheper, Rik J., van den Eertwegh, Alfons J. M., Gerritsen, Winald R., and de Gruijl, Tanja D.

Published
2013
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11. Local delivery of low-dose anti–CTLA-4 to the melanoma lymphatic basin leads to systemic Treg reduction and effector T cell activation.

Author

van Pul, Kim M., Notohardjo, Jessica C. L., Fransen, Marieke F., Koster, Bas D., Stam, Anita G. M., Chondronasiou, Dafni, Lougheed, Sinéad M., Bakker, Joyce, Kandiah, Vinitha, van den Tol, M. Petrousjka, Jooss, Karin, Vuylsteke, Ronald J. C. L. M., van den Eertwegh, Alfons J. M., and de Gruijl, Tanja D.

Subjects
T cells, SENTINEL lymph node biopsy, REGULATORY T cells, SENTINEL lymph nodes, T cell differentiation, MELANOMA
Abstract

Preclinical studies show that locoregional CTLA-4 blockade is equally effective in inducing tumor eradication as systemic delivery, without the added risk of immune-related side effects. This efficacy is related to access of the CTLA-4 blocking antibodies to tumor-draining lymph nodes (TDLNs). Local delivery of anti–CTLA-4 after surgical removal of primary melanoma, before sentinel lymph node biopsy (SLNB), provides a unique setting to clinically assess the role of TDLN in the biological efficacy of locoregional CTLA-4 blockade. Here, we have evaluated the safety, tolerability, and immunomodulatory effects in the SLN and peripheral blood of a single dose of tremelimumab [a fully human immunoglobulin gamma-2 (IgG2) mAb directed against CTLA-4] in a dose range of 2 to 20 mg, injected intradermally at the tumor excision site 1 week before SLNB in 13 patients with early-stage melanoma (phase 1 trial; NCT04274816). Intradermal delivery was safe and well tolerated and induced activation of migratory dendritic cell (DC) subsets in the SLN. It also induced profound and durable decreases in regulatory T cell (Treg) frequencies and activation of effector T cells in both SLN and peripheral blood. Moreover, systemic T cell responses against NY-ESO-1 or MART-1 were primed or boosted (N = 7), in association with T cell activation and central memory T cell differentiation. These findings indicate that local administration of anti–CTLA-4 may offer a safe and promising adjuvant treatment strategy for patients with early-stage melanoma. Moreover, our data demonstrate a central role for TDLN in the biological efficacy of CTLA-4 blockade and support TDLN-targeted delivery methods. Under the skin: Although systemic immune checkpoint blockade (ICB) displays therapeutic efficacy in cancers, it induces immune-related adverse events (irAEs). Avoiding irAEs is crucial for effective ICB. Van Pul et al. performed a phase 1 clinical trial testing the effects of an intradermal injection of anti–CTLA-4 at the site of primary tumor excision in patients with early-stage melanoma. Seven of 13 patients immunologically responded to the treatment, with little to no irAEs. Responders had more tumor antigen–specific T cells in the blood, increased migratory DC activation in the sentinel lymph node (SLN), and decreased Tregs in both the SLN and blood. Thus, intradermal anti–CTLA-4 after primary tumor excision in melanoma induced a favorable immune response and has promise as a treatment option for patients with early-stage melanoma. [ABSTRACT FROM AUTHOR]

Published
2022
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13. Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells

Author

Glykofridis, Iris E, primary, Knol, Jaco C, additional, Balk, Jesper A, additional, Westland, Denise, additional, Pham, Thang V, additional, Piersma, Sander R, additional, Lougheed, Sinéad M, additional, Derakhshan, Sepide, additional, Veen, Puck, additional, Rooimans, Martin A, additional, van Mil, Saskia E, additional, Böttger, Franziska, additional, Poddighe, Pino J, additional, van de Beek, Irma, additional, Drost, Jarno, additional, Zwartkruis, Fried JT, additional, de Menezes, Renee X, additional, Meijers-Heijboer, Hanne EJ, additional, Houweling, Arjan C, additional, Jimenez, Connie R, additional, and Wolthuis, Rob MF, additional

Published
2021
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14. Author response: Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells

Author

Glykofridis, Iris E, primary, Knol, Jaco C, additional, Balk, Jesper A, additional, Westland, Denise, additional, Pham, Thang V, additional, Piersma, Sander R, additional, Lougheed, Sinéad M, additional, Derakhshan, Sepide, additional, Veen, Puck, additional, Rooimans, Martin A, additional, van Mil, Saskia E, additional, Böttger, Franziska, additional, Poddighe, Pino J, additional, van de Beek, Irma, additional, Drost, Jarno, additional, Zwartkruis, Fried JT, additional, de Menezes, Renee X, additional, Meijers-Heijboer, Hanne EJ, additional, Houweling, Arjan C, additional, Jimenez, Connie R, additional, and Wolthuis, Rob MF, additional

Published
2020
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16. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells

Author

de Bruin, Renée C G, Veluchamy, John P., Lougheed, Sinéad M, Schneiders, Famke L., Lopez-Lastra, Silvia, Lameris, Roeland, Stam, Anita G M, Sebestyen, Zsolt, Kuball, Jürgen, Molthoff, Carla F M, Hooijberg, Erik, Roovers, Rob C., Santo, James P.Di, van Bergen En Henegouwen, Paul M P, Verheul, Henk M. W., de Gruijl, Tanja D, van Vliet, Hans J, de Bruin, Renée C G, Veluchamy, John P., Lougheed, Sinéad M, Schneiders, Famke L., Lopez-Lastra, Silvia, Lameris, Roeland, Stam, Anita G M, Sebestyen, Zsolt, Kuball, Jürgen, Molthoff, Carla F M, Hooijberg, Erik, Roovers, Rob C., Santo, James P.Di, van Bergen En Henegouwen, Paul M P, Verheul, Henk M. W., de Gruijl, Tanja D, and van Vliet, Hans J

Published
2017

17. Highly specific and potently activating V gamma 9V delta 2-T cell specific nanobodies for diagnostic and therapeutic applications

Author

de Bruin, Renée C G, Lougheed, Sinéad M., van der Kruk, Liza, Stam, Anita G., Hooijberg, Erik, Roovers, Rob C., van Bergen en Henegouwen, Paul M P, Verheul, Henk M W, de Gruijl, Tanja D., van der Vliet, Hans J., Celbiologie, Sub Cell Biology, CCA - Cancer immunology, Medical oncology laboratory, AII - Cancer immunology, Medical oncology, Pathology, Celbiologie, and Sub Cell Biology

Subjects
0301 basic medicine, Adoptive cell transfer, T-Lymphocytes, medicine.medical_treatment, T cell, Immunology, Antibody Affinity, VHH, Biology, Gamma delta T cells, Jurkat cells, Jurkat Cells, 03 medical and health sciences, Immune system, Cancer immunotherapy, Antibody Specificity, medicine, Animals, Humans, Immunology and Allergy, Flow cytometry, Cells, Cultured, Cancer, Bispecific monoclonal antibody, Immunomagnetic Separation, Single-domain antibody fragment, Reproducibility of Results, Receptors, Antigen, T-Cell, gamma-delta, Immunotherapy, Single-Domain Antibodies, Immunohistochemistry, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Microscopy, Fluorescence, biology.protein, Nanobody, MACS, Antibody, Camelids, New World, Immunocytochemistry
Abstract

Vγ9Vδ2-T cells constitute the predominant subset of γδ-T cells in human peripheral blood and have been shown to play an important role in antimicrobial and antitumor immune responses. Several efforts have been initiated to exploit these cells for cancer immunotherapy, e.g. by using phosphoantigens, adoptive cell transfer, and by a bispecific monoclonal antibody based approach. Here, we report the generation of a novel set of Vγ9Vδ2-T cell specific VHH (or nanobody). VHH have several advantages compared to conventional antibodies related to their small size, stability, ease of generating multispecific molecules and low immunogenicity. With high specificity and affinity, the anti-Vγ9Vδ2-T cell receptor VHHs are shown to be useful for FACS, MACS and immunocytochemistry. In addition, some VHH were found to specifically activate Vγ9Vδ2-T cells. Besides being of possible immunotherapeutic value, these single domain antibodies will be of great value in the further study of this important immune effector cell subset.

Published
2016

18. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells

Author

de Bruin, Renée C. G., primary, Veluchamy, John P., additional, Lougheed, Sinéad M., additional, Schneiders, Famke L., additional, Lopez-Lastra, Silvia, additional, Lameris, Roeland, additional, Stam, Anita G., additional, Sebestyen, Zsolt, additional, Kuball, Jürgen, additional, Molthoff, Carla F. M., additional, Hooijberg, Erik, additional, Roovers, Rob C., additional, Santo, James P. Di, additional, van Bergen en Henegouwen, Paul M. P., additional, Verheul, Henk M. W., additional, de Gruijl, Tanja D., additional, and van der Vliet, Hans J., additional

Published
2017
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20. Highly specific and potently activating Vγ9Vδ2-T cell specific nanobodies for diagnostic and therapeutic applications

Author

de Bruin, Renée C G, Lougheed, Sinéad M., van der Kruk, Liza, Stam, Anita G., Hooijberg, Erik, Roovers, Rob C., van Bergen en Henegouwen, Paul M P, Verheul, Henk M W, de Gruijl, Tanja D., van der Vliet, Hans J., de Bruin, Renée C G, Lougheed, Sinéad M., van der Kruk, Liza, Stam, Anita G., Hooijberg, Erik, Roovers, Rob C., van Bergen en Henegouwen, Paul M P, Verheul, Henk M W, de Gruijl, Tanja D., and van der Vliet, Hans J.

Published
2016

21. Sensing of latent EBV infection through exosomal transfer of 5'pppRNA

Author

dI&I I&I-1, LS Virologie, Baglio, S Rubina, van Eijndhoven, Monique A J, Koppers-Lalic, Danijela, Berenguer, Jordi, Lougheed, Sinéad M, Gibbs, Susan, Léveillé, Nicolas, Rinkel, Rico N P M, Hopmans, Erik S, Swaminathan, Sankar, Verkuijlen, Sandra A W M, Scheffer, George L, van Kuppeveld, Frank J M, de Gruijl, Tanja D, Bultink, Irene E M, Jordanova, Ekaterina S, Hackenberg, Michael, Piersma, Sander R, Knol, Jaco C, Voskuyl, Alexandre E, Wurdinger, Thomas, Jiménez, Connie R, Middeldorp, Jaap M, Pegtel, D Michiel, dI&I I&I-1, LS Virologie, Baglio, S Rubina, van Eijndhoven, Monique A J, Koppers-Lalic, Danijela, Berenguer, Jordi, Lougheed, Sinéad M, Gibbs, Susan, Léveillé, Nicolas, Rinkel, Rico N P M, Hopmans, Erik S, Swaminathan, Sankar, Verkuijlen, Sandra A W M, Scheffer, George L, van Kuppeveld, Frank J M, de Gruijl, Tanja D, Bultink, Irene E M, Jordanova, Ekaterina S, Hackenberg, Michael, Piersma, Sander R, Knol, Jaco C, Voskuyl, Alexandre E, Wurdinger, Thomas, Jiménez, Connie R, Middeldorp, Jaap M, and Pegtel, D Michiel

Published
2016

22. Abstract B138: Single low-dose administration of anti-CTLA-4/tremelimumab at the tumor excision site boosts systemic antitumor immunity in early-stage melanoma patients: Results from a Phase-1 study

Author

Stam, Anita G.M., primary, Pul, Kim M. van, additional, Koster, Bas D., additional, Chondronasiou, Dafni, additional, Lougheed, Sinéad M., additional, Tol, M. Petrousjka van den, additional, Jooss, Karin, additional, Vuylsteke, Ronald J.C.L.M., additional, Eertwegh, Alfons J.M. van den, additional, and Gruijl, Tanja D. de, additional

Published
2016
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24. Myeloid derived suppressor and dendritic cell subsets are related to clinical outcome in prostate cancer patients treated with prostate GVAX and ipilimumab

Author

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

Published
2014
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26. IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation

Author

Lindenberg, Jelle J., primary, Oosterhoff, Dinja, additional, Sombroek, Claudia C., additional, Lougheed, Sinéad M., additional, Hooijberg, Erik, additional, Stam, Anita G. M., additional, Santegoets, Saskia J. A. M., additional, Tijssen, Henk J., additional, Buter, Jan, additional, Pinedo, Herbert M., additional, van den Eertwegh, Alfons J. M., additional, Scheper, Rik J., additional, Koenen, Hans J. P. M., additional, van de Ven, Rieneke, additional, and de Gruijl, Tanja D., additional

Published
2013
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27. Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

Author

Oosterhoff, Dinja, primary, Heusinkveld, Moniek, additional, Lougheed, Sinéad M., additional, Kosten, Ilona, additional, Lindstedt, Malin, additional, Bruijns, Sven C. M., additional, van Es, Thomas, additional, van Kooyk, Yvette, additional, van der Burg, Sjoerd H., additional, and de Gruijl, Tanja D., additional

Published
2013
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28. Functional characterization of a STAT3-dependent dendritic cell-derived CD14+cell population arising upon IL-10-driven maturation

Author

Lindenberg, Jelle J., primary, van de Ven, Rieneke, additional, Lougheed, Sinéad M., additional, Zomer, Anoek, additional, Santegoets, Saskia JAM, additional, Griffioen, Arjan W., additional, Hooijberg, Erik, additional, van den Eertwegh, Alfons J.M., additional, Thijssen, Victor L., additional, Scheper, Rik J., additional, Oosterhoff, Dinja, additional, and de Gruijl, Tanja D., additional

Published
2013
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29. Abstract 1229: Pre-existing NY-ESO-1-specific T cell reactivity is associated with improved clinical outcome in castration resistant prostate cancer patients treated with Prostate GVAX and ipilimumab.

Author

Stam, Anita GM, primary, Santegoets, Saskia JAM, additional, van den Eertwegh, Alfons JM, additional, Scheper, Rik J., additional, Lougheed, Sinéad M., additional, Gall, Helen, additional, Jooss, Karin, additional, Sacks, Natalie, additional, Harding, Thomas, additional, Hege, Kristen, additional, Lowy, Israel, additional, Gnjatic, Sacha, additional, Wolchok, Jedd D., additional, Gerritsen, Winald R., additional, and de Gruijl, Tanja D., additional

Published
2013
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30. T cell profiling reveals high CD4+CTLA-4+ T cell frequency as dominant predictor for survival after Prostate GVAX/ipilimumab treatment

Author

Santegoets, Saskia J. A. M., primary, Stam, Anita G. M., additional, Lougheed, Sinéad M., additional, Gall, Helen, additional, Scholten, Petra E. T., additional, Reijm, Martine, additional, Jooss, Karin, additional, Sacks, Natalie, additional, Hege, Kristen, additional, Lowy, Israel, additional, Cuillerot, Jean-Marie, additional, von Blomberg, B. Mary E., additional, Scheper, Rik J., additional, van den Eertwegh, Alfons J. M., additional, Gerritsen, Winald R., additional, and de Gruijl, Tanja D., additional

Published
2012
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32. Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation

Author

van de Ven, Rieneke, primary, van den Hout, Mari F. C. M., additional, Lindenberg, Jelle J., additional, Sluijter, Berbel J. R., additional, van Leeuwen, Paul A. M., additional, Lougheed, Sinéad M., additional, Meijer, Sybren, additional, van den Tol, M. Petrousjka, additional, Scheper, Rik J., additional, and de Gruijl, Tanja D., additional

Published
2011
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33. Glioblastoma-induced inhibition of Langerhans cell differentiation from CD34+precursors is mediated by IL-6 but unaffected by JAK2/STAT3 inhibition

Author

van Cruijsen, Hester, primary, Oosterhoff, Dinja, additional, Lindenberg, Jelle J, additional, Lougheed, Sinéad M, additional, Fehres, Cynthia, additional, Weijers, Karin, additional, van Boerdonk, Robert, additional, Giaccone, Giuseppe, additional, Scheper, Rik J, additional, Hoekman, Klaas, additional, and de Gruijl, Tanja D, additional

Published
2011
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34. Abstract 5512: Immune correlates of clinical response and survival in castration-resistant prostate cancer patients treated with prostate GVAX and anti-CTLA4 immunotherapy

Author

Santegoets, Saskia J.A.M., primary, van den Eertwegh, Alfons J.M., additional, Stam, Anita G.M., additional, Scheper, Rik J., additional, Lougheed, Sinéad M., additional, Scholten, Petra E.T., additional, von Blomberg, Mary B.M.E., additional, Gall, Helen, additional, Jooss, Karin, additional, Nguyen, Minh C., additional, Harding, Tom, additional, Sacks, Natalie, additional, Hege, Kristen, additional, Lowy, Israel, additional, Chin, Kevin, additional, Gerritsen, Winald R., additional, and de Gruijl, Tanja D., additional

Published
2011
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38. CD40-targeted adenoviral gene transfer to dendritic cells through the use of a novel bispecific single-chain Fv antibody enhances cytotoxic T cell activation

Author

Brandão, Joana G., primary, Scheper, Rik J., additional, Lougheed, Sinéad M., additional, Curiel, David T., additional, Tillman, Bryan W., additional, Gerritsen, Winald R., additional, van den Eertwegh, Alfons J.M., additional, Pinedo, Herbert M., additional, Haisma, Hidde J., additional, and de Gruijl, Tanja D., additional

Published
2003
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39. Prolonged Maturation and Enhanced Transduction of Dendritic Cells Migrated from Human Skin Explants After In Situ Delivery of CD40-Targeted Adenoviral Vectors

Author

de Gruijl, Tanja D., primary, Luykx-de Bakker, Sylvia A., additional, Tillman, Bryan W., additional, van den Eertwegh, Alfons J. M., additional, Buter, Jan, additional, Lougheed, Sinéad M., additional, van der Bij, Gerben J., additional, Safer, A. Mahmoud, additional, Haisma, Hidde J., additional, Curiel, David T., additional, Scheper, Rik J., additional, Pinedo, Herbert M., additional, and Gerritsen, Winald R., additional

Published
2002
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41. Prostanoids Play a Major Role in the Primary Tumor-Induced Inhibition of Dendritic Cell Differentiation

Author

Sombroek, Claudia C., primary, Stam, Anita G. M., additional, Masterson, Allan J., additional, Lougheed, Sinéad M., additional, Schakel, Marcel J. A. G., additional, Meijer, Chris J. L. M., additional, Pinedo, Herbert M., additional, van den Eertwegh, Alfons J. M., additional, Scheper, Rik J., additional, and de Gruijl, Tanja D., additional

Published
2002
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42. Functional characterization of a STAT3-dependent dendritic cell-derived CD14+ cell population arising upon IL-10-driven maturation.

Author

Lindenberg, Jelle J., van de Ven, Rieneke, Lougheed, Sinéad M., Zomer, Anoek, Santegoets, Saskia J.A.M., Griffioen, Arjan W., Hooijberg, Erik, Van den Eertwegh, Alfons J.M., Thijssen, Victor L., Scheper, Rik J., Oosterhoff, Dinja, and de Gruijl, Tanja D.

Subjects
INTERLEUKIN-10, CELL proliferation, DENDRITIC cells, MACROPHAGE activation, CYTOKINES
Abstract

Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a+ DCs found in the human skin to CD14+CD141+ macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14- and CD14+ DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14+ DCs were phenotypically characterized by a low maturation state as well as by high levels of BDCA3 and DC-SIGN, and as such they closely resembled CD14+ cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14+ DCs were found to express high levels of B7-H1 on the cell surface, to secrete low levels of IL- 12p70, to preferentially induce TH2 cells, to have a lower allogeneic TH cell and tumor antigen-specific CD8+ T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14+ counterparts, CD14- monocyte-derived DCs retained allogeneic TH priming capacity but induced a functionally anergic state as they completely abolished the release of effector cytokines. Transcriptional and cytokine release profiling studies indicated a more profound angiogenic and pro-invasive signature of CD14+ DCs as compared with DCs matured in standard conditions or CD14- DCs matured in the presence of IL-10. Importantly, signal transducer and activator of transcription 3 (STAT3) depletion by RNA interference prevented the development of the IL-10-associated CD14+ phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention. [ABSTRACT FROM AUTHOR]

Published
2013
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43. A CD34+human cell line model of myeloid dendritic cell differentiation: evidence for a CD14+CD11b+Langerhans cell precursor

Author

Santegoets, Saskia J. A. M., Masterson, Allan J., Sluis, Pieter C., Lougheed, Sinéad M., Fluitsma, Donna M., Eertwegh, Alfons J. M., Pinedo, Herbert M., Scheper, Rik J., and Gruijl, Tanja D.

Abstract

The study of early events in dendritic cell (DC) differentiation is hampered by the lack of homogeneous primary cell systems that allow the study of cytokine‐driven, transitional DC differentiation steps. The CD34+acute myeloid leukemia cell line MUTZ‐3 displays a unique ability to differentiate into interstitial DC (IDC) and Langerhans cells (LC) in a cytokine‐dependent manner. Phenotypic characterization revealed MUTZ‐3 to consist of three distinct subpopulations. Small CD34+CD14−CD11b−progenitors constitute the proliferative compartment of the cell line with the ability to differentiate through a CD34−CD14−CD11b+stage to ultimately give rise to a morphologically large, nonproliferating CD14+CD11bhiprogeny. These CD14+CD11bhicells were identified as common, immediate myeloid DC precursors with the ability to differentiate into LC and IDC, exhibiting characteristic and mutually exclusive expression of Langerin and DC‐specific ICAM‐grabbing nonintegrin, respectively. The identity of the MUTZ‐3‐derived LC subset was confirmed further by the presence of Birbeck granules. We conclude that the MUTZ‐3 cell line provides a ready and continuous supply of common myeloid precursors, which should facilitate further study of the ontogeny of myeloid DC lineages.

Published
2006
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44. A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.

Author

de Bruin, Renée C. G., Veluchamy, John P., Lougheed, Sinéad M., Schneiders, Famke L., Lopez-Lastra, Silvia, Lameris, Roeland, Stam, Anita G., Sebestyen, Zsolt, Kuball, Jürgen, Molthoff, Carla F. M., Hooijberg, Erik, Roovers, Rob C., Santo, James P. Di, van Bergen en Henegouwen, Paul M. P., Verheul, Henk M. W., de Gruijl, Tanja D., and van der Vliet, Hans J.

Subjects
CANCER immunotherapy, T cells, CANCER treatment, THERAPEUTICS
Abstract

Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. Vγ9Vδ2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of Vγ9Vδ2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both Vγ9Vδ2-T cells and EGFR induced potent Vγ9Vδ2-T cell activation and subsequent tumor cell lysis bothin vitroand in anin vivomouse xenograft model. Tumor cell lysis was independent ofKRASandBRAFtumor mutation status and common Vγ9Vδ2-T cell receptor sequence variations. In combination with the conserved monomorphic nature of the Vγ9Vδ2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients. [ABSTRACT FROM PUBLISHER]

Published
2018
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45. Functional characterization of a STAT3-dependent dendritic cell-derived CD14 + cell population arising upon IL-10-driven maturation.

Author

Lindenberg JJ, van de Ven R, Lougheed SM, Zomer A, Santegoets SJ, Griffioen AW, Hooijberg E, van den Eertwegh AJ, Thijssen VL, Scheper RJ, Oosterhoff D, and de Gruijl TD

Abstract

Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a + DCs found in the human skin to CD14 + CD141 + macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14 - and CD14 + DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14 + DCs were phenotypically characterized by a low maturation state as well as by high levels of BDCA3 and DC-SIGN, and as such they closely resembled CD14 + cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14 + DCs were found to express high levels of B7-H1 on the cell surface, to secrete low levels of IL-12p70, to preferentially induce TH2 cells, to have a lower allogeneic TH cell and tumor antigen-specific CD8 + T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14 + counterparts, CD14 - monocyte-derived DCs retained allogeneic TH priming capacity but induced a functionally anergic state as they completely abolished the release of effector cytokines. Transcriptional and cytokine release profiling studies indicated a more profound angiogenic and pro-invasive signature of CD14 + DCs as compared with DCs matured in standard conditions or CD14 - DCs matured in the presence of IL-10. Importantly, signal transducer and activator of transcription 3 (STAT3) depletion by RNA interference prevented the development of the IL-10-associated CD14 + phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention.

Published
2013
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