Dissecting and modulating reactive anti-tumor immunity in human cancers

Reinvigoration of tumor-specific T cells by cancer immunotherapies, in particular PD-1/PD-L1 blocking agents, has been the most important innovation in the treatment of patients with cancer. Nevertheless, durable clinical benefit is currently limited to a small number of patients. At present, the immunological alterations that occur in human cancers upon PD-1 blockade are not well understood. Using patient-derived organotypic tumor models, we investigate how tumor immune composition and architecture influence immunotherapy response and how distinct treatments can change immune activity in a tumor. The observed immunotherapy-induced changes can then be linked to the inherent qualities of a tumor and its infiltrating immune populations, thereby contributing to the identification of determinants for effective response to immunotherapy and to the development of novel treatment strategies.