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4. TGF-β promotes microtube formation in glioblastoma through thrombospondin 1

Author

Joseph, Justin V, primary, Magaut, Capucine R, additional, Storevik, Simon, additional, Geraldo, Luiz H, additional, Mathivet, Thomas, additional, Latif, Md Abdul, additional, Rudewicz, Justine, additional, Guyon, Joris, additional, Gambaretti, Matteo, additional, Haukas, Frida, additional, Trones, Amalie, additional, Rømo Ystaas, Lars A, additional, Hossain, Jubayer A, additional, Ninzima, Sandra, additional, Cuvellier, Sylvain, additional, Zhou, Wenjing, additional, Tomar, Tushar, additional, Klink, Barbara, additional, Rane, Lalit, additional, Irving, Bronwyn K, additional, Marrison, Joanne, additional, O’Toole, Peter, additional, Wurdak, Heiko, additional, Wang, Jian, additional, Di, Zhang, additional, Birkeland, Even, additional, Berven, Frode S, additional, Winkler, Frank, additional, Kruyt, Frank A E, additional, Bikfalvi, Andreas, additional, Bjerkvig, Rolf, additional, Daubon, Thomas, additional, and Miletic, Hrvoje, additional

Published
2021
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5. TGF-β promotes microtube formation in glioblastoma through thrombospondin 1.

Author

Joseph, Justin V, Magaut, Capucine R, Storevik, Simon, Geraldo, Luiz H, Mathivet, Thomas, Latif, Md Abdul, Rudewicz, Justine, Guyon, Joris, Gambaretti, Matteo, Haukas, Frida, Trones, Amalie, Ystaas, Lars A Rømo, Hossain, Jubayer A, Ninzima, Sandra, Cuvellier, Sylvain, Zhou, Wenjing, Tomar, Tushar, Klink, Barbara, Rane, Lalit, and Irving, Bronwyn K

Published
2022
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6. TGF-β promotes microtube formation in glioblastoma through Thrombospondin 1

Author

Joseph, Justin V., primary, Magaut, Capucine R., additional, Storevik, Simon, additional, Geraldo, Luiz H., additional, Mathivet, Thomas, additional, Latif, Md Abdul, additional, Rudewicz, Justine, additional, Guyon, Joris, additional, Gambaretti, Matteo, additional, Haukas, Frida, additional, Trones, Amalie, additional, Rømo Ystaas, Lars A., additional, Hossain, Jubayer A., additional, Sandra Ninzima, S, additional, Zhou, Wenjing, additional, Tomar, Tushar, additional, Klink, Barbara, additional, Rane, Lalit, additional, Irving, Bronwyn K., additional, Marrison, Joanne, additional, O’Toole, Peter, additional, Wurdak, Heiko, additional, Wang, Jian, additional, Di, Zhang, additional, Winkler, Frank, additional, Kruyt, Frank A. E., additional, Bikfalvi, Andreas, additional, Bjerkvig, Rolf, additional, Daubon, Thomas, additional, and Miletic, Hrvoje, additional

Published
2021
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7. CSIG-37. TGF-β PROMOTES MEMBRANE TUBE FORMATION IN GLIOBLASTOMA THAT CONTRIBUTES TO INVASION AND THERAPY RESISTANCE

Author

Joseph, Justin, primary, Grosch, Julia, additional, Tomar, Tushar, additional, Klink, Barbara, additional, Daubon, Thomas, additional, Rane, Lalit, additional, Solecki, Gergely, additional, Hasan-Olive, Mahdi, additional, Hossain, Jubayer, additional, Latif, Abdul, additional, Ninzima, Sandra, additional, Bergersen, Linda, additional, Tardito, Saverio, additional, Kruyt, Frank, additional, Bjerkvig, Rolf, additional, Winkler, Frank, additional, and Miletic, Hrvoje, additional

Published
2017
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8. Tumor-infiltrating lymphocytes (TILs) from patients with glioma

Author

Liu, Zhenjiang, primary, Meng, Qingda, additional, Bartek, Jiri, additional, Poiret, Thomas, additional, Persson, Oscar, additional, Rane, Lalit, additional, Rangelova, Elena, additional, Illies, Christopher, additional, Peredo, Inti Harvey, additional, Luo, Xiaohua, additional, Rao, Martin Vijayakumar, additional, Robertson, Rebecca Axelsson, additional, Dodoo, Ernest, additional, and Maeurer, Markus, additional

Published
2017
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10. Both high and low levels of cellular Epstein-Barr virus DNA in blood identify failure after hematologic stem cell transplantation in conjunction with acute GVHD and type of conditioning

Author

Li, Qin, primary, Rane, Lalit, additional, Poiret, Thomas, additional, Zou, Jiezhi, additional, Magalhaes, Isabelle, additional, Ahmed, Raija, additional, Du, Ziming, additional, Vudattu, Nalini, additional, Meng, Qingda, additional, Gustafsson-Jernberg, Åsa, additional, Winiarski, Jacek, additional, Ringdén, Olle, additional, Maeurer, Markus, additional, Remberger, Mats, additional, and Ernberg, Ingemar, additional

Published
2016
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11. NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma.

Author

Liu, Zhenjiang, Poiret, Thomas, Persson, Oscar, Meng, Qingda, Rane, Lalit, Bartek, Jiri, Karbach, Julia, Altmannsberger, Hans-Michael, Illies, Christopher, Luo, Xiaohua, Harvey-Peredo, Inti, Jäger, Elke, Dodoo, Ernest, and Maeurer, Markus

Subjects
GLIOMA treatment, SURVIVIN (Protein), CELLULAR therapy, ANTINEOPLASTIC agents, IMMUNOHISTOCHEMISTRY
Abstract

The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1 protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and 9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could detect antigen-specific IFN-γ responses in 25% blood samples for NY-ESO-1 and 30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable targets for anticancer-directed T-cells for the biological therapy of patients with glioma. [ABSTRACT FROM AUTHOR]

Published
2018
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12. Enhanced tumor-infiltrating lymphocytes (eTIL) for cellular therapy of patients with pancreatic cancer or glioblastoma

Author

Meng, Qingda, primary, Liu, Zhenjiang, additional, Maeurer, Markus, additional, Rangelova, Elena, additional, Ambati, Aditya, additional, Poiret, Thomas, additional, Rane, Lalit, additional, Xie, Shanshan, additional, Jiri, Bartek, additional, Verbeke, Caroline, additional, Persson, Oscar, additional, Löhr, Matthias, additional, Segersvärd, Ralf, additional, and Dodoo, Ernest, additional

Published
2015
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13. IL-2, IL-15 and IL-21 expand T cells for targeted adoptive therapy

Author

Liu, Zhenjiang, primary, Meng, Qingda, additional, Maeurer, Markus, additional, Rangelova, Elena, additional, Poiret, Thomas, additional, Robertson, Rebecca, additional, Ambati, Aditya, additional, Rane, Lalit, additional, Bartek, Jiri, additional, Verbeke, Caroline, additional, Persson, Oscar, additional, Löhr, Matthias, additional, Segersvärd, Ralf, additional, and Dodoo, Ernest, additional

Published
2015
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14. TCR+CD4−CD8− T cells in Antigen-specific MHC Class I–restricted T-cell Responses After Allogeneic Hematopoietic Stem Cell Transplantation

Author

Ahmed, Raija K., primary, Poiret, Thomas, additional, Ambati, Aditya, additional, Rane, Lalit, additional, Remberger, Mats, additional, Omazic, Birgitta, additional, Vudattu, Nalini K., additional, Winiarski, Jacek, additional, Ernberg, Ingemar, additional, Axelsson-Robertson, Rebecca, additional, Magalhaes, Isabelle, additional, Castelli, Chiara, additional, Ringden, Olle, additional, and Maeurer, Markus, additional

Published
2014
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16. Reduced plasma levels of soluble interleukin-7 receptor during graft-versus-host disease (GVHD) in children and adults

Author

Poiret, Thomas, primary, Rane, Lalit, additional, Remberger, Mats, additional, Omazic, Birgitta, additional, Gustafsson-Jernberg, Åsa, additional, Vudattu, Nalini Kumar, additional, Ahmed, Raija, additional, Ernberg, Ingemar, additional, Winiarski, Jacek, additional, Magalhaes, Isabelle, additional, Ringden, Olle, additional, and Maeurer, Markus, additional

Published
2014
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17. Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic

Author

Magalhaes, Isabelle, primary, Eriksson, Mikael, additional, Linde, Charlotte, additional, Muhammad, Rashid, additional, Rane, Lalit, additional, Ambati, Aditya, additional, Axelsson-Robertson, Rebecca, additional, Khalaj, Bahareh, additional, Alvarez-Corrales, Nancy, additional, Lapini, Giulia, additional, Montomoli, Emanuele, additional, Linde, Annika, additional, Pedersen, Nancy L, additional, and Maeurer, Markus, additional

Published
2014
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22. Frontline Science: Placenta-derived decidual stromal cells alter IL-2R expression and signaling in alloantigen-activated T cells

Author

Erkers, Tom, Solders, Martin, Verleng, Lotte, Bergström, Cecilia, Stikvoort, Arwen, Rane, Lalit, Nava, Silvia, Ringdén, Olle, and Kaipe, Helen

Abstract

Decidual stromal cells increase concentrations of IL-2 in the allogeneic setting, and reduce the IL-2 receptor expression and signaling in T cells. This study investigated how stromal cells affect the IL-2 pathway in alloantigen-activated T cells. We found that decidual stromal cells (DSCs) from term placentas promoted a high production of IL-2 in cultures with alloantigen-activated T cells. The intensity of expression of cluster of differentiation 25 (CD25; IL-2Ra) on T cells was increased by DSCs, whereas the frequency and intensity of expression of the signaling subunits CD122 (IL-2Rß) and CD132 (IL-2R?c) were reduced. Consequently, uptake of IL-2 and STAT5 phosphorylation (pSTAT5) was abrogated. DSCs also decreased the proportion of pSTAT5+T cells in response to IL-15, which also use CD122 for signaling. Addition of DSCs to the allogeneic cultures did not increase the expression of programmed death 1 (PD-1) or CD95, indicating that they did not promote T cell exhaustion. However, exogenous recombinant (r)IL-2 in similar concentrations in the same setting increased the expression of CD95 and down-regulated CD122 in T cells. The antiproliferative effect of sirolimus (SRL) and cyclosporine A (CsA), which target the IL-2 signaling pathway, was diminished by DSCs in vitro. To conclude, DSCs affect IL-2 production and IL-2R expression and signaling, which may contribute to the stromal cell-mediated immune modulation and phenotype shift seen in activated T cells. Altered proliferation in cultures when combining DSCs and SRL or CsA may be of clinical importance, as stromal cells are used in trials for acute inflammation and are often used in combination with conventional immunosuppressive therapies.

Published
2017
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25. Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer

Author

Meng, Qingda, Liu, Zhenjiang, Rangelova, Elena, Poiret, Thomas, Ambati, Aditya, Rane, Lalit, Xie, Shanshan, Verbeke, Caroline, Dodoo, Ernest, Del Chiaro, Marco, Löhr, Matthias, Segersvärd, Ralf, and Maeurer, Markus J.

Abstract

Supplemental Digital Content is available in the text.Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor-infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry. Cytotoxicity was measured using a Chromium 51 release assay, and reactivity of TILs against autologous tumor cells was detected by INF-γ production (ELISA). TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis. TCR Vβ was determined by flow cytometry and TCR clonality was gauged measuring the CDR3 region length by PCR analysis and subsequent sequencing. We could reliably obtain TILs from 17/17 patients with a majority of CD8+T cells. CD3+CD8+, CD3+CD4+, and CD3+CD4−CD8−[double-negative (DN) T cells] resided predominantly in central (CD45RA−CCR7+) and effector (CD45RA−CCR7−) memory subsets. CD8+TILs tested uniformly positive for LAG-3 (about 100%), whereas CD4+TILs showed only up to 12% LAG-3+staining and PD-1 showed a broad expression pattern in TILs from different patients. TILs from individual patients recognized strongly (up to 11.9% and 8.2% in CD8+) NY-ESO-1, determined by ICS, or mesothelin, determined respectively by TNF-α and IFN-γ production. Twelve of 17 of CD8+TILs showed preferential expansion of certain TCR Vβ families (eg, 99.2% Vβ13.2 in CD8+TILs, 77% in the Vβ1, 65.9% in the Vβ22, and 63.3% in the Vβ14 family). TCR CDR3 analysis exhibited monoclonal or oligoclonal TCRs, some of them (eg, CD8+Vβ13.2) reacting strongly against autologous tumor defined by INF-γ production or by cytotoxicity. We have optimized methods for generating pancreatic cancer–specific TILs that can be used for adoptive cellular therapy of patients with pancreatic cancer.

Published
2016
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26. Tumor-infiltrating lymphocytes (TILs) from patients with glioma.

Author

Liu Z, Meng Q, Bartek J Jr, Poiret T, Persson O, Rane L, Rangelova E, Illies C, Peredo IH, Luo X, Rao MV, Robertson RA, Dodoo E, and Maeurer M

Abstract

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4 + , CD8 + , as well as CD3 + CD4 - CD8 - T cells with a predominant central memory CD45RA - CCR7 + phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8 + TIL, with low (1.25%) frequencies in CD4 + T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.

Published
2016
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27. TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation.

Author

Ahmed RK, Poiret T, Ambati A, Rane L, Remberger M, Omazic B, Vudattu NK, Winiarski J, Ernberg I, Axelsson-Robertson R, Magalhaes I, Castelli C, Ringden O, and Maeurer M

Subjects
Adolescent, Adult, Antigens, Viral immunology, CD4 Antigens metabolism, CD8 Antigens metabolism, Female, Follow-Up Studies, HLA-A2 Antigen metabolism, HLA-A24 Antigen metabolism, Humans, Interleukin-8 metabolism, Jurkat Cells, Male, Middle Aged, Receptors, Antigen, T-Cell, alpha-beta genetics, Transcriptome, Transplantation, Homologous, Young Adult, Epstein-Barr Virus Infections immunology, Hematopoietic Stem Cell Transplantation, Herpesvirus 4, Human immunology, Receptors, Antigen, T-Cell, alpha-beta metabolism, T-Lymphocytes immunology
Abstract

Human TCRαβ(+) CD4(-)CD8(-) double-negative (DN) T cells represent a minor subset in peripheral blood, yet are important in infectious diseases and autoimmune responses. We examined the frequency of DN T cells in 17 patients after allogeneic hematopoietic stem cell transplantation (aHSCT) at 1, 2, 3, 6, and 12 months post-aHSCT and show that these cells increase early after aHSCT and decrease with time after aHSCT. DN T cells reside in the terminally differentiated effector (CD45RA(+)CCR7(-)) T-cell population and are polyclonal, determined by T-cell receptor Vβ CDR3 analysis. Gene expression analysis of ex vivo sorted DN T cells showed a distinct set of gene expression, including interleukin-8, as compared with CD4(+) or CD8(+) T cells. DN T cells contributed to MHC class I-restricted EBV-directed immune responses, defined by antigen-specific cytokine production and by detection of HLA-A*02:01-restricted EBV BMLF-1 (GLCTLVAML), LMP-2A (CLGGLLTMV), and HLA-A*24:02-restricted EBV BRLF-1 (DYCNVLNKEF) and EBNA3 (RYSIFFDY)-specific T cells. We created retroviral-transfected Jurkat cell lines with a Melan-A/MART-1-specific TCR(+) and the CD8α chain to study TCR(+) DN T cells in response to their nominal MHC class I/peptide ligand. We show that DN T cells exhibit increased TCRζ chain phosphorylation as compared with the TCR(+)CD8(+) transgenic T-cell line. DN T cells contribute to antigen-specific T-cell responses and represent an effector T-cell population that may be explored in immunotherapeutic approaches against viral infections or transformed cells.

Published
2014
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