Cancer stem cell dynamics in tumor progression and metastasis: Is the microenvironment to blame?

Stem cells are defined by their self-renewal capacity and the ability to give rise to all differentiated progeny necessary for one specific organ. These two characteristics are also inherent in cancer stem cells (CSCs), which are thought to be the only subpopulation within a tumor endowed with tumorigenic potential. CSCs combine many features that render cancer one of the leading causes of death in the Western world: metastasis, tumor recurrence, and therapy refractoriness. Strikingly, CSCs are not a fixed entity, but differentiated tumor cells are able to revert to a stem-like state. Thus, CSCs are not only intrinsically programmed to fulfill their detrimental roles, but are orchestrated by stromal cells residing in their vicinity and forming the CSC niche. Yet, this relationship is not a one-way road: CSCs are able to manipulate stromal cells to their needs, not only in the primary tumor, but also in distant organs and thus prime the foreign soil for their arrival by inducing a premetastatic niche. The suggested plasticity between the differentiation states of cancer cells and the regulation by microenvironmental cues provides new starting-points for novel cancer therapies. (C) 2012 Elsevier Ireland Ltd. All rights reserve

Author Correction: Tissue patrol by resident memory CD8+ T cells in human skin (Nature Immunology, (2019), 20, 6, (756-764), 10.1038/s41590-019-0404-3)

In the version of this article initially published, the molecular-weight cutoff of the filtering unit was incorrectly given as 10,000 kDa; the correct value is 10 kDa. The incorrect value was given in Methods section “Generation of fluorescently labeled nanobodies,” in the sentences beginning “Purity of recombinant nanobody was assessed by SDS–PAGE ...” and “Subsequently, the unbound fraction was added ....” In the same section, the buffer composition for the hepta-mutant sortase incorrectly included 10 mM CaCl 2. The correct text is “To this end, purified GGGC–AF594 (80 μM) was incubated with purified nanobody–LPETGG-6×His (5 μM) and penta-mutant (5 M) or hepta-mutant (7 M) sortase (0.8 μM) for 2 h at 4 °C in 50 mM Tris pH 8 and 150 mM NaCl, and in the case of the penta-mutant, 10 mM CaCl 2 was added (sortase was produced in house according to a previously described protocol using sonification instead of French press 40). The errors have been corrected in the HTML and PDF versions of the article

Tissue patrol by resident memory CD8+ T cells in human skin

Emerging data show that tissue-resident memory T (TRM) cells play an important protective role at murine and human barrier sites. TRM cells in the epidermis of mouse skin patrol their surroundings and rapidly respond when antigens are encountered. However, whether a similar migratory behavior is performed by human TRM cells is unclear, as technology to longitudinally follow them in situ has been lacking. To address this issue, we developed an ex vivo culture system to label and track T cells in fresh skin samples. We validated this system by comparing in vivo and ex vivo properties of murine TRM cells. Using nanobody labeling, we subsequently demonstrated in human ex vivo skin that CD8+ TRM cells migrated through the papillary dermis and the epidermis, below sessile Langerhans cells. Collectively, this work allows the dynamic study of resident immune cells in human skin and provides evidence of tissue patrol by human CD8+ TRM cells