@article{BruttelWischhusen2014,
  author    = {Bruttel, Valentin S. and Wischhusen, J{\"o}rg},
  title     = {Cancer Stem Cell Immunology: Key to Understanding Tumorigenesis and Tumor Immune Escape?},
  series = {Frontiers in Immunology},
  volume    = {5},
  journal   = {Frontiers in Immunology},
  number    = {360},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2014.00360},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120699},
  year      = {2014},
  abstract  = {Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation. Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow straight into overt tumors. These criteria would be fulfilled by CSCs. Stem cells are pluripotent, immune-privileged, and long-living, but depend on specialized niches. Thus, latent tumors may be maintained by a niche-constrained reservoir of long-living CSCs that are exempt from immunosurveillance while niche-independent and more immunogenic daughter cells are constantly eliminated. The small subpopulation of CSCs is often held responsible for tumor initiation, metastasis, and recurrence. Experimentally, this hypothesis was supported by the observation that only this subset can propagate tumors in non-obese diabetic/scid mice, which lack T and B cells. Yet, the concept was challenged when an unexpectedly large proportion of melanoma cells were found to be capable of seeding complex tumors in mice which further lack NK cells. Moreover, the link between stem cell-like properties and tumorigenicity was not sustained in these highly immunodeficient animals. In humans, however, tumor-propagating cells must also escape from immune-mediated destruction. The ability to persist and to initiate neoplastic growth in the presence of immunosurveillance - which would be lost in a maximally immunodeficient animal model - could hence be a decisive criterion for CSCs. Consequently, integrating scientific insight from stem cell biology and tumor immunology to build a new concept of "CSC immunology" may help to reconcile the outlined contradictions and to improve our understanding of tumorigenesis.},
  language  = {en}
}
@article{HaeuslerdelBarrioDiessneretal.2014,
  author    = {H{\"a}usler, Sebastian F. M. and del Barrio, Itsaso Montalb{\´a}n and Diessner, Joachim and Stein, Roland G. and Strohschein, Jenny and H{\"o}nig, Arnd and Dietl, Johannes and Wischhusen, J{\"o}rg},
  title     = {Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion},
  series = {American Journal of Translational Research},
  volume    = {6},
  journal   = {American Journal of Translational Research},
  number    = {2},
  issn      = {1943-8141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120016},
  pages     = {129-139},
  year      = {2014},
  abstract  = {The ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the \(A_{2A}\) adenosine receptor (ADORA2A) on T and NK cells. The current study investigates the potential therapeutic use of the specific anti CD39- and anti CD73-antibodies A1 (CD39) and 7G2 (CD73) as these two ectonucleotidases are overexpressed in ovarian cancer (OvCA). As expected, NK cell cytotoxicity against the human ovarian cancer cell lines OAW-42 or SK-OV-3 was significantly increased in the presence of A1 or 7G2 antibody. While this might partly be due to antibody-dependent cell-mediated cytotoxicity, a luciferase-dependent assay for quantifying biologically active adenosine further showed that A1 and 7G2 can inhibit CD39 and CD73-dependent adenosine-generation. In turn, the reduction in adenosine levels achieved by addition of A1 and 7G2 to OAW-42 or SK-OV-3 cells was found to de-inhibit the proliferation of \(CD4^+\) T cells in coculture with OvCA cells. Likewise, blocking of CD39 and CD73 on OvCA cells via A1 and 7G2 led to an increased cytotoxicity of alloreactive primed T cells. Thus, antibodies like A1 and 7G2 could improve targeted therapy in ovarian cancer not only by specifically labeling overexpressed antigens but also by blocking adenosine-dependent immune evasion in this immunogenic malignancy.},
  language  = {en}
}
@article{SieglPrustyKarunakaranetal.2014,
  author    = {Siegl, Christine and Prusty, Bhupesh K. and Karunakaran, Karthika and Wischhusen, J{\"o}rg and Rudel, Thomas},
  title     = {Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection},
  series = {Cell Reports},
  volume    = {9},
  journal   = {Cell Reports},
  number    = {3},
  issn      = {2211-1247},
  doi       = {10.1016/j.celrep.2014.10.004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118200},
  pages     = {918-929},
  year      = {2014},
  abstract  = {Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.},
  language  = {en}
}
@article{KellerLeidingerVogeletal.2014,
  author    = {Keller, Andreas and Leidinger, Petra and Vogel, Britta and Backes, Christina and ElSharawy, Abdou and Galata, Valentina and Mueller, Sabine C. and Marquart, Sabine and Schrauder, Michael G. and Strick, Reiner and Bauer, Andrea and Wischhusen, J{\"o}rg and Beier, Markus and Kohlhaas, Jochen and Katus, Hugo A. and Hoheisel, J{\"o}rg and Franke, Andre and Meder, Benjamin and Meese, Eckart},
  title     = {miRNAs can be generally associated with human pathologies as exemplified for miR-144*},
  series = {BMC MEDICINE},
  volume    = {12},
  journal   = {BMC MEDICINE},
  issn      = {1741-7015},
  doi       = {10.1186/s12916-014-0224-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114349},
  pages     = {224},
  year      = {2014},
  abstract  = {Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95\% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.},
  language  = {en}
}