TY - JOUR AU - Zhang, Y. AU - Tang, C. AU - Span, P.N. AU - Rowan, A.E. AU - Aalders, T. AU - Schalken, J.A. AU - Adema, G.J. AU - Kouwer, P.H.J. AU - Zegers, M.M.P. AU - Ansems, M. PY - 2020 UR - https://hdl.handle.net/2066/227470 TI - Polyisocyanide Hydrogels as a Tunable Platform for Mammary Gland Organoid Formation SN - 2198-3844 IS - iss. 18 JF - Advanced Science VL - vol. 7 DO - https://doi.org/10.1002/advs.202001797 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/227470/227470.pdf?sequence=1 ER - TY - JOUR AU - Büll, C. AU - Boltje, T.J. AU - Balneger, N. AU - Weischer, S. AU - Wassink, M. AU - Gemst, J. van AU - Bloemendal, V.R.L.J. AU - Boon, L. AU - Vlag, J. van der AU - Heise, T. AU - Brok, M.H. den AU - Adema, G.J. PY - 2018 UR - https://hdl.handle.net/2066/193642 AB - Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to the immunosuppressive microenvironment and tumor immune evasion. However, the mechanisms by which these sugars modulate antitumor immunity as well as therapeutic strategies directed against them are limited. Here we report that intratumoral injections with a sialic acid mimetic Ac53FaxNeu5Ac block tumor sialic acid expression in vivo and suppress tumor growth in multiple tumor models. Sialic acid blockade had a major impact on the immune cell composition of the tumor, enhancing tumor-infiltrating natural killer cell and CD8(+) T-cell numbers while reducing regulatory T-cell and myeloid regulatory cell numbers. Sialic acid blockade enhanced cytotoxic CD8(+) T-cell-mediated killing of tumor cells in part by facilitating antigen-specific T-cell-tumor cell clustering. Sialic acid blockade also synergized with adoptive transfer of tumor-specific CD8(+) T cells in vivo and enhanced CpG immune adjuvant therapy by increasing dendritic cell activation and subsequent CD8(+) T-cell responses. Collectively, these data emphasize the crucial role of sialic acids in tumor immune evasion and provide proof of concept that sialic acid blockade creates an immune-permissive tumor microenvironment for CD8(+) T-cell-mediated tumor immunity, either as single treatment or in combination with other immune-based intervention strategies.Significance: Sialic acid sugars function as important modulators of the immunosuppressive tumor microenvironment that limit potent antitumor immunity.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg Cancer Res; 78(13); 3574-88. (c)2018 AACR. TI - Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell-Mediated Tumor Immunity EP - 3588 SN - 0008-5472 IS - iss. 13 SP - 3574 JF - Cancer Research VL - vol. 78 DO - https://doi.org/10.1158/0008-5472.CAN-17-3376 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/193642/193642.pdf?sequence=1 ER - TY - JOUR AU - Eleveld-Trancikova, D. AU - Triantis, V. AU - Moulin, V. AU - Looman, M.W.G. AU - Wijers-Rouw, M.J.P. AU - Fransen, J.A.M. AU - Lemckert, A.A. AU - Havenga, M.J. AU - Figdor, C.G. AU - Janssen, R.A.J. AU - Adema, G.J. PY - 2005 UR - https://hdl.handle.net/2066/48204 AB - Recently, we described the molecular identification of dendritic cell-specific TrAnsMembrane protein (DC-STAMP), a multimembrane-spanning protein preferentially expressed by human DC (hDC). In this report, we describe the identification and expression profile of the murine homologue of DC-STAMP (mDC-STAMP) as well as the characterization of the DC-STAMP protein. The results demonstrate that mDC-STAMP is over 90% homologous to hDC-STAMP and is also preferentially expressed by DC in vitro and ex vivo. mDC-STAMP expression is enhanced by interleukin-4 and down-regulated upon DC maturation. Analysis of differently tagged DC-STAMP proteins further demonstrates that hDC-STAMP and mDC-STAMP are glycosylated and primarily localize to an intracellular compartment. Applying confocal microscopy and electron microscopy, we demonstrate that hDC-STAMP localizes to the endoplasmic reticulum (ER) in human embryonic kidney 293 cells as well as hDC transduced with an adenovirus encoding hDC-STAMP-green fluorescent protein fusion protein. These data imply that DC-STAMP may exert its effect in the ER. TI - The dendritic cell-derived protein DC-STAMP is highly conserved and localizes to the endoplasmic reticulum. EP - 343 SN - 0741-5400 IS - iss. 3 SP - 337 JF - Journal of Leukocyte Biology VL - vol. 77 DO - http://dx.doi.org/10.1189/jlb.0804441 ER - TY - JOUR AU - Wansink, D.G. AU - Peters, W.J.M AU - Schaafsma, I. AU - Sutmuller, R.P.M. AU - Oerlemans, F.T.J.J. AU - Adema, G.J. AU - Wieringa, B. AU - Zee, C.E.E.M. van der AU - Hendriks, W.J.A.J. PY - 2004 UR - https://hdl.handle.net/2066/57323 AB - Mouse PTP-BL is a large, nontransmembrane protein tyrosine phosphatase of unclear physiological function that consists of a KIND domain, a FERM domain, five PDZ domains, and a COOH-terminal catalytic PTP domain. PTP-BL and its human ortholog PTP-BAS have been proposed to play a role in the regulation of microfilament dynamics, cytokinesis, apoptosis, and neurite outgrowth. To investigate the biological function of PTP-BL enzyme activity, we have generated mice that lack the PTP-BL PTP moiety. These PTP-BL(DeltaP/DeltaP) mice are viable and fertile and do not present overt morphological alterations. Although PTP-BL is expressed in most hematopoietic cell lineages, no alterations of thymocyte development in PTP-BL(DeltaP/DeltaP) mice could be detected. Sciatic nerve lesioning revealed that sensory nerve recovery is unaltered in these mice. In contrast, a very mild but significant impairment of motor nerve repair was observed. Our findings exclude an essential role for PTP-BL as a phosphotyrosine phosphatase and rather are in line with a role as scaffolding or anchoring molecule. TI - Mild impairment of motor nerve repair in mice lacking PTP-BL tyrosine phosphatase activity. EP - 60 SN - 1094-8341 IS - iss. 1 SP - 50 JF - Physiological Genomics VL - vol. 19 DO - https://doi.org/10.1152/physiolgenomics.00079.2004 ER -