Immune signatures within the tumor and in the peripheral blood as prognostic/predictive biomarkers in breast cancer
PI in Germany: Graham Pawelec; PI in Greece: Costas Baxevanis.
German Federal Ministry for Research and Development (BMBF, 2014-2016):
There is now accumulating evidence to suggest that the quantity, quality and spatial distribution of immune cells within the tumor (immune contexture and immune score; IC/IS) may have a greater prognostic value than standard TNM staging. Recent exciting studies of colorectal cancers have underlined the significance of IC/IS as prognostic markers. However, in order to validate the general concept of IC/IS as a prognostic factor, this needs to be characterized in other tumor types.
Here, we propose to explore the prognostic impact of IC/IS in patients with breast carcinoma (BC). Our studies will include for the first time
- prospective analyses to identify IC/IS in patients with newly-diagnosed BC with clinical follow-up and
- comparative quantification and phenotyping of circulating T lymphocytes responding to tumor antigens overexpressed in BC.
It is useful to compare peripheral with intra-tumoral immune markers for longitudinal follow-up and ease of sample access. In addition, we will perform retrospective analyses to correlate IC/IS with clinical outcome in patients with BC who were treated between 2000 and 2008. The results from our study will document whether IC/IS are reliable prognostic immunological markers for BC, and the results from the retrospective analyses will additionally provide information on the role of intratumoral T cells as immune predictive biomarkers for patient outcome following standard chemotherapeutic regimes combined with targeted therapies (e.g. trastuzumab). Our work will also place strong emphasis on the role of tumor-specific circulating T cells serving as intermediate and/or endpoint surrogates for clinical efficacy and for selecting patients most likely to benefit from peptide-based vaccinations.