@article{HeuserGototPiotrowskietal.2017,
  author    = {Heuser, Christoph and Gotot, Janine and Piotrowski, Eveline Christina and Philipp, Marie-Sophie and Courr{\`e}ges, Christina Johanna Felicia and Otte, Martin Sylvester and Guo, Linlin and Schmid-Burgk, Jonathan Leo and Hornung, Veit and Heine, Annkristin and Knolle, Percy Alexander and Garbi, Natalio and Serfling, Edgar and Evaristo, C{\´e}sar and Thaiss, Friedrich and Kurts, Christian},
  title     = {Prolonged IKK\(\beta\) Inhibition Improves Ongoing CTL Antitumor Responses by Incapacitating Regulatory T Cells},
  series = {Cell Reports},
  volume    = {21},
  journal   = {Cell Reports},
  number    = {3},
  doi       = {10.1016/j.celrep.2017.09.082},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173643},
  pages     = {578-586},
  year      = {2017},
  abstract  = {Regulatory T cells (Tregs) prevent autoimmunity but limit antitumor immunity. The canonical NF-\(\kappa\)B signaling pathway both activates immunity and promotes thymic Treg development. Here, we report that mature Tregs continue to require NF-\(\kappa\)B signaling through I\(\kappa\)B-kinase \(\beta\) (IKK\(\beta\)) after thymic egress. Mice lacking IKK\(\beta\) in mature Tregs developed scurfy-like immunopathology due to death of peripheral FoxP3\(^+\) Tregs. Also, pharmacological IKK\(\beta\) inhibition reduced Treg numbers in the circulation by ~50\% and downregulated FoxP3 and CD25 expression and STAT5 phosphorylation. In contrast, activated cytotoxic T lymphocytes (CTLs) were resistant to IKK\(\beta\) inhibition because other pathways, in particular nuclear factor of activated T cells (NFATc1) signaling, sustained their survival and expansion. In a melanoma mouse model, IKK\(\beta\) inhibition after CTL cross-priming improved the antitumor response and delayed tumor growth. In conclusion, prolonged IKK\(\beta\) inhibition decimates circulating Tregs and improves CTL responses when commenced after tumor vaccination, indicating that IKK\(\beta\) represents a druggable checkpoint.},
  language  = {en}
}
@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}
}