Control of disease recurrence by tumor-infiltrating T cells in ovarian cancer.
How does the immune system evolve during initial stages of ovarian cancer versus later recurrence of the disease? Our aim is to identify tumor antigens as unique targets for immuno-therapy in advanced ovarian cancer.
|Project Leaders||Robert Holt , Brad Nelson, Peter Watson, John Webb|
US Army, Department of Defense
Rosettes of dividing T-cells
The presence of T cells within the initial ovarian tumor is correlated with favorable clinical outcomes (increased patient survival), but it is not clear how these T cells, having failed to stop the growth of the primary tumor, can prevent tumor recurrence. We speculate that the initial T cell response evident in primary tumors expands with the addition of new T cell responses triggered by chemotherapy. Specifically, we suspect that the mutational effects of chemotherapy generate new tumor antigens that trigger a second wave of CD8+ T cell responses, which in turn promote favorable clinical outcomes. Answering this question is not only of scientific interest, it is also critical to the development of effective immuno-therapy against recurrent ovarian cancers. If we are to successfully treat patients with cytokines, vaccines or T cell infusions, it is essential to define which specific T cell responses need to be enhanced.
Recent Publications from this Research Team:
Freeman JD, Warren RL, Webb JR, Nelson BH, Holt RA (2009) Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing.Genome Res.19: 1817-1824. [Epub ahead of print, Jul 13]
Milne K, Köbel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors PLoS One. 4(7):e6412.
Milne K, Barnes RO, Girardin A, Mawer MA, Nesslinger NJ, Ng A, Nielsen JS, Sahota R, Tran E, Webb JR, Wong MQ, Wick DA, Wray A, McMurtrie E, Köbel M, Kalloger SE, Gilks CB, Watson PH, Nelson BH (2008) Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer. PLoS One.3(10):e3409. [Epub 2008 Oct 15.]
For all project related inquires please contact us.
Joanne Johnson, Projects Manager
Genome Sciences Centre, BC Cancer Agency
Phone: (604)675-8150 x 7901