Cancer Stem Cell Immunology: Key to Understanding Tumorigenesis and Tumor Immune Escape?

Please always quote using this URN: urn:nbn:de:bvb:20-opus-120699
  • 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 beCancer 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.show moreshow less

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Metadaten
Author: Valentin S. Bruttel, Jörg Wischhusen
URN:urn:nbn:de:bvb:20-opus-120699
Document Type:Journal article
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Language:English
Parent Title (English):Frontiers in Immunology
ISSN:1664-3224
Year of Completion:2014
Volume:5
Issue:360
DOI:https://doi.org/10.3389/fimmu.2014.00360
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25120546
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:cancer stem cell immunology; cancer stem cells; latency; tumor dormancy; tumor immune escape
tumor immunology; tumor immunosurveillance; tumor-propagating cells
Release Date:2016/02/15
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung