What they want
The research will use metastatic 4MOSC1 (ICB responsive) and 4MOSC2 (ICB non-responsive) orthotopic mouse models of head and neck cancer. Aim 1 will interrogate whether defects in the S1P/S1PR1 lymphocyte migration axis in metLN affect Tpex responses to ICB using in vivo and in vitro methods. Aim 2 will evaluate whether activation of Tpex in metLN confers cell-intrinsic defects affecting their capacity to differentiate, survive, and signal through their T cell receptor, also using in vivo and in vitro methods. Aim 3 will identify mechanisms by which metastases in tdLN affect the polarization of CD4 T cells and activation of DC proximal to Tpex, utilizing spatial proteomic and transcriptomic tools.
Technical requirements
- Mass cytometry
- Spatial proteomics
- Metastatic 4MOSC1 and 4MOSC2 orthotopic mouse models of head and neck cancer
- In vivo methods
- In vitro methods
- Spatial transcriptomic tools
Key personnel
- Dr. Matthew Spitzer (expert in CD8 T cell and lymph node biology, systems immunology, high-dimensional single cell analyses)
- Dr. Jason Cyster (world-class scientist, discovered lymphocyte trafficking mechanism)
- Dr. Karin Pelka (cancer immunologist, expertise in spatial biological tools)
- Fellowship trainee
