Background: γδ T cells are cytotoxic and capable of killing cancer cells, independent of MHC-mediated target cell recognition, however, it is not clear how the cells function in metastatic breast cancer.
Aims: We aim to determine the function of γδ T cell subsets in metastatic breast cancer, to uncover methods to utilise these cells for immunotherapy and diagnostics.
Methods: We utilised opal multiplex immunohistochemistry to score γδ T cell abundance and phenotype in 35 patient tissues. Primary and metastatic tissue scoring was completed to determine infiltration and phenotype of γδ T cells in tumour regions and surrounding areas. Alongside, we used co-culture methods to interrogate the ability of γδ T cells to kill breast cancer cell lines of varying metastatic potential.
Results: Compared to primary tumours, total γδ T cell numbers are depleted in metastatic tissues, and phenotype suggests loss in cytotoxicity, indicating the cells are differentially regulated in metastatic sites. This is mirrored in co-culture assays, with resistance to γδ T cell-mediated killing observed in cell lines of higher metastatic potential.
Conclusions: γδ T cells are lacking in metastatic breast cancer patients and have lost markers of cytotoxicity, inferring loss of function in progressive disease, which is confirmed with in vitro assays. Through further study, we will identify a pathway to manipulate these cells, increasing their abundance and restoring cytotoxic function of γδ T cells in progressive disease.