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

Reyk Hillert1, Anne Gieseler1,2, Andreas Krusche1

  • 1Molecular Pattern Recognition Research Group, Medical Faculty, OvG University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany.

Scientific Reports
|January 14, 2016
PubMed

Insights

Researchers discovered a novel mechanism called SPIKE where skin cancer traps CD8 T cells. This involves keratinocyte projections interconnecting T cells, hindering immune surveillance against tumors.

Area of Science:

  • Immunology
  • Dermatology
  • Cancer Biology

Background:

  • CD8 T lymphocytes are crucial for immune surveillance of tumors.
  • Tumor immune evasion is a significant challenge in cancer treatment.
  • The tumor microenvironment plays a critical role in immune suppression.

Purpose of the Study:

  • To investigate the immune contexture in human skin cancer.
  • To identify mechanisms of immune evasion within the tumor microenvironment.
  • To understand how CD8 T cells fail in cancer surveillance.

Main Methods:

  • Utilized imaging cycler microscopy to analyze immune cells in skin cancer.
  • Mapped over 7,000 distinct cell surface-associated multi-protein assemblies.
  • Employed combinatorial geometry-based analysis for high-functional resolution.

Main Results:

  • Discovered a novel mechanism of T cell trapping in the epidermis, termed SPIKE.
  • SPIKE involves suprabasal keratinocyte projections interconnecting CD8 T cells.
  • Identified initiation involving infrabasal T and dendritic cells connecting to suprabasal keratinocytes and T lymphocytes across a fractured basal lamina.

Conclusions:

  • SPIKE represents a previously unknown mechanism of immune evasion in skin cancer.
  • This mechanism physically traps CD8 T cells, impairing anti-tumor immune surveillance.
  • Understanding SPIKE may offer new therapeutic targets for enhancing cancer immunity.