@article{GrimmigMoenchKreckeletal.2016, author = {Grimmig, Tanja and Moench, Romana and Kreckel, Jennifer and Haack, Stephanie and Rueckert, Felix and Rehder, Roberta and Tripathi, Sudipta and Ribas, Carmen and Chandraker, Anil and Germer, Christoph T. and Gasser, Martin and Waaga-Gasser, Ana Maria}, title = {Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer}, series = {International Journal of Molecular Sciences}, volume = {17}, journal = {International Journal of Molecular Sciences}, number = {12}, doi = {10.3390/ijms17122060}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165743}, pages = {2060}, year = {2016}, abstract = {Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.}, language = {en} } @article{LangenhorstHaackGoebetal.2018, author = {Langenhorst, Daniela and Haack, Stephanie and G{\"o}b, Selina and Uri, Anna and L{\"u}hder, Fred and Vanhove, Bernhard and H{\"u}nig, Thomas and Beyersdorf, Niklas}, title = {CD28 costimulation of T helper 1 cells enhances cytokine release in vivo}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {1060}, doi = {10.3389/fimmu.2018.01060}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176726}, year = {2018}, abstract = {Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred in vitro generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2\(^{+}\)) and then either blocked CD28-ligand interactions with Fab fragments of the anti-CD28 monoclonal antibody (mAb) E18 or deleted CD28 expression using inducible CD28 knock-out OT-II mice as T cell donors. After injection of ovalbumin protein in adjuvant into the recipient mice we observed that systemic interferon (IFN)γ release strongly depended on CD28 costimulation of the Th1 cells, while secondary clonal expansion was not reduced in the absence of CD28 costimulation. For human memory CD4\(^{+}\) T cell responses we also noted that cytokine release was reduced upon inhibition of CD28 costimulation. Together, our data highlight the so far underestimated role of CD28 costimulation for the reactivation of fully differentiated CD4\(^{+}\) T cells.}, language = {en} }