Thomas Spies, PhD

Thomas Spies, PhD


University of Hamburg, 1981, MS (Biology and Biochemistry)
University of Hamburg, 1984, PhD (Microbiology)

Research Focus:

Our research interests are centered on the stimulatory NKG2D lymphocyte receptor on natural killer (NK) cells and T cells, which interacts with multiple ligands that are selectably induced in viral infections, certain autoimmune diseases, and most notably in cancer. Recognition by NKG2D of its ligands induced on malignant cells by oncogenesis-associated cellular stress responses, is well known to promote tumor immune surveillance at early stages of tumor growth. However, immunosuppressive tactics of progressing tumors defuse NKG2D functionality, thus stifling this arm of the immune response. Moreover, in a surprising conceptual twist, cancer cells can co-opt expression of NKG2D itself for their own benefit, complementing the presence of its ligands for autonomous stimulation of oncogenic signaling, tumor growth and malignant progression. Recent findings suggest that NKG2D promotes cancer plasticity with differentiation towards mesenchymal and migratory phenotypes and stem-like attributes. Cancer cell NKG2D may thus have the capacity to drive high malignancy traits underlying metastatic disease.

Clinical Expertise:

Expression of NKG2D ligands has been associated with poor clinical outcomes in various cancers. Our findings suggest that in fact cancer cell expression of the NKG2D receptor itself may represent the main culprit determining negative prognoses. The significance of NKG2D as a prognostic factor is explored in breast and ovarian cancer. In addition to solid cancers, preliminary data suggest a potentially similar role of NKG2D in AML.

Current Studies:

  • Regulation and immunologic effects of NKG2D-bearing immunosuppressive CD4 T cells in Lupus
  • Coupling of cellular stress responses to NKG2D ligand expression in cancer
  • Tumor immune evasion mediated by shedding of soluble NKG2D ligands
  • NKG2D receptor signaling in cancer cells and resultant effects on tumor growth and progression
  • Regulation by NKG2D of epithelial-mesenchymal transitions and induction and/or maintenance of cancer stem cell traits

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Thomas Spies, PhD

Contact Information

(206) 667-6940
(206) 667-6124
Additional contact

Mail Stop: D1-100