Ex vivo culture to evaluate dynamic changes in the tumor microenvironment following durvalumab treatment

While the tumor microenvironment (TME) is critical to the mechanism of action of anti-PD-1/PD-L1 checkpoint inhibitions, limitations exist to understand this using in vitro and in vivo models. With bladder (BCa) and prostate (PCa) cancer representing cancer with respectively strong and poor responses to PD-1/PD-L1 inhibition, we used ex vivo culture of fresh patient cancer tissue to better understand changes in the TME following durvalumab therapy, specifically the macrophage phenotype.Fresh prostate or bladder biopsies from 70 patients were cultured with durvalumab or isotype control. Flow cytometry assessed a panel of myeloid cell markers.In BCa samples, there was a significant difference, after durvalumab treatment, in PD-L1 expression on non-immune cells and macrophages and increased reactive oxygen species (ROS) production by myeloid cells in BCa. In PCa samples, there was a significant decrease in PD-L1 expression on non-immune and immune cells and increased ROS production by macrophages. Concomitantly, we observed a significant decrease in phagocytosis activity in immune cells and macrophages in prostate biopsies.Our detailed cytometric analysis of ex vivo cultured BCa and PCa biopsies demonstrated changes in macrophage phenotype after durvalumab treatment. This study shows ex vivo culture can ascertain trends in tumor immune cell responses to immunotherapy.