4.7 Article

Large molecular systems landscape uncovers T cell trapping in human skin cancer

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep19012

Keywords

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Funding

  1. Klaus Tschira Foundation (KTS)
  2. Deutsche Forschungsgemeinschaft (DFG) [Schu627/10-1]
  3. BMBF (grant CELLECT)
  4. MBF (grant NBL3)
  5. BMBF (grant NGFN2)
  6. BMBF (grant NGFNplus)
  7. DFG-Innovationskolleg [INK15]
  8. EU IMAGINT [Health-F5-2011-259881]
  9. Human Toponome Project
  10. Berliner Krebsgesellschaft [WAFF2000824]

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Immune surveillance of tumour cells is an important function of CD8 T lymphocytes, which has failed in cancer for reasons still unknown in many respect but mainly related to cellular processes in the tumour microenvironment. Applying imaging cycler microscopy to analyse the immune contexture in a human skin cancer we could identify and map 7,000 distinct cell surface-associated multi-protein assemblies. The resulting combinatorial geometry-based high-functional resolution led to discovery of a mechanism of T cell trapping in the epidermis, which involves SPIKE, a network of suprabasal keratinocyte projections piercing and interconnecting CD8 T cells. It appears initiated by clusters of infrabasal T and dendritic cells connected via cell projections across a fractured basal lamina to suprabasal keratinocytes and T lymphocytes.

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