As the most common site of breast cancer metastasis, understanding the dynamic changes within the bone microenvironment could be exploited for preventative measures. Monteran et al. recently identified key interactions between granulocytes and T cells that promote an immunosuppressive bone microenvironment that is permissive to metastasis.

Owing to the ability of MDSCs to inhibit cytotoxic T lymphocyte (CTL) functionality, the authors next characterized CD8+ T cells isolated from the core and periphery of the bone metastasis, and those from early metastasis or those from normal mice. Core CD8+ T cells expressed increased levels of multiple granzymes and had high expression of dysfunction markers including Pdcd1, Fasl, Tigit, Lag3 and Ctla4. Moreover, CD3+CD4+CD25+ T cells were found to be transcriptionally reprogrammed into immunosuppressive regulatory T (Treg) cells. Together this indicates that infiltrating T cells become dysfunctional and/or exhausted due to the immunosuppressive microenvironment induced by MDSCs and Treg cells.