@article{HaakeHaackSchaeferetal.2023, author = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg}, title = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39817-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333}, year = {2023}, abstract = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.}, language = {en} } @article{MauelerBarnekowEigenbrodtetal.1988, author = {Maueler, W. and Barnekow, A. and Eigenbrodt, E. and Raulf, F. and Falk, H. F. and Telling, A. and Schartl, Manfred}, title = {Different regulation of oncogene expression in tumor and embryonal cells of Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86240}, year = {1988}, abstract = {Melanoma formation in the poeciliid fish Xiphophorus is mediated primarily by a cellular oncogene, designated Tu. Elimination of Tu-specific genes releases the transforming function of Tu and leads to melanoma formation. Southern blot analyses revealed a tight linkage of a v-erb B related gene to the Tu-locus and Northern blot analyses of RNA of solid melanomas indicated a coordinated deregulation and for mutational activation of several oncogenes. In order to get a better insight into the regulation of oncogene expression in normal and transformed cells of Xiphophorus, we studied the expression of Xsrc, Xras, Xmyc, Xerb A, Xsis, and the v-erb B related gene in a melanoma derived cell line (PSM) and an embryonic cell line (A2) under conditions of low growth factor supply. Both celllines express the Xsrc, Xmyc, and Xras genes, while PSM cells in addition express the v-erb B related gene and A2 cells the Xsis gene. In PSM cells serum deprivation leads to an accumulation of most of the oncogene mRNAs analysed. This is most apparent for a 5.0 kb transcript of the v-erb B related gene, probably due to an increase in transcript stability. The levels of these mRNAs returned to normal within 2h after stimulation with 10\% fetal calf serum. At the protein level we observed an initial decrease followed by an increase of the n-p60c-src kinase (the protein product of tbe Xsrc gene) activity in cells deprived of serum. Serum stimulation restored a normal pp60"-src kinase activity. In contrast serum deprivation of A2 cells reduced the transcript amounts of each of the oncogenes analysed. The same holds true for one beta-tubulin transcript, while the level of a second beta-tubulin transcript was unaffected. Serum stimulation led to a reactivation of Xras and Xsrc after a delay of approximately 48b. The pp60(c-src) kinase activity was found to be 6-10 times lower as compared to the PSM cells and did not differ between serum deprived and serum stimulated cells. Enzyme activities and isoenzyme patterns of several glycolytic enzymes were found to be not affected by serum deprivation and stimulation in both celllines.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{FrankeBergerFalketal.1974, author = {Franke, Werner W. and Berger, S. and Falk, Heinz and Spring, H. and Scheer, Ulrich and Trendelenburg, Michael F. and Schweiger, H. G. and Herth, W.}, title = {Morphology of the nucleo-cytoplasmic interactions during the development of Acetabularia cells. I. The vegetative phase}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32363}, year = {1974}, abstract = {The ultrastructure of th e growin g and ma turing primary nucleus of Acetabularia medite rranea and Acetabularia major has been studied with the use of various fi xation procedures. Particular interest has been focused on the deta ils of the nuclear periphery and the perinuclear region. It is demonstrated that early in nuclear grow th a characteristic perinucl ear structura l complex is formed which is, among the eukaryotic cells, unique to Acetabularia and re lated genera. This perinuclear system consists essentially of a) the nuclear envelope with a very hi gh pore frequency and various pore complex assoc iat ion s w ith granular and/or threadlike structures some of which are continuous with the nucleolus; b) an approx imate ly 100 nm thick intermediate zone densely filled with a filam entOus material and occasional sma ll membraneous structures from which the typical cytOplasmic and nuclear organe lles and particles are excl ud ed ; c) an adjacent Iacunar labyrinthum which is interrupted by many plasmatic junction channels between the intermed iate zone and the free cytOplasm; d) numerous dense perinuclear bodies in the juxtanuclear cytOplasm which a re especia lly frequent at the junction channels and reveal a composition of aggregated fibrillar and granul ar structures; e) very dense exclusively fibrill ar agg regates which occur either in assoc iation with t he perinuclear region of the lacunar labyrinthum or, somewhat further out, in the cytOplasmic strands between the bra nches of the lacun ar labyrinthum in the form of slender, characteristic rods or "sausages".}, language = {en} }