Prof. Stefani Spranger

The goal of the Spranger lab is to understand the molecular mechanisms of a range of tumor cell-intrinsic, tissue-specific or environmental factors directly impacting the interaction between cancer and the immune system. Understanding which permutations affect the anti-tumor immune response will answer thus far unanswered questions on the interplay between the immune system with the tumor and will facilitate the development of new rational therapeutic approaches.

Over the last decade cancer immunotherapies, first and foremost checkpoint blockade therapy (anti-CTLA4 and anti-PD-1/PD-L1) has revolutionized cancer treatment. Despite the recent advances it should be noted that only a fraction of cancer patients responds towards immunotherapeutic interventions. Even for cancer types with a high response rate, only a fraction of patients are responding. The presence of CD8+ T cells, so-called cytolytic T cells, within the tumor microenvironment, is known to be the discriminating factor for the response towards checkpoint blockade. Most cancer types can be subdivided into T cell-inflamed and non-T cell-inflamed groups, based on the presence of CD8+ T cells.

Thus far our knowledge on factors contributing to the exclusion of immune cells is limited. Studies in melanoma have provided insights that tumor cell-intrinsic activation of certain signaling pathways, WNT/β-catenin and PI3K, are linked to the loss of T cell infiltration. Specifically, activation of β-catenin results in a local reduction of a dendritic cell subset specialized in the activation of CD8+ T cells. Furthermore, depletion of only this subset of dendritic cells renders the previously T cell-inflamed into a non-T cell-inflamed tumor microenvironment, illustrating the complexity of the tumor microenvironment.

The Spranger lab aims to understand what additional factors contribute to T cell exclusion from the tumor microenvironment, including tumor cell-intrinsic, tissue-macroenvironmental or environmental factors (e.g. infections). The lab focuses on lung cancer and pancreatic cancer, representing immunotherapy-sensitive and resistant cancer types, respectively.

By understanding the factors contributing to a productive or malfunctioning anti-tumor immune response, factor determining the presence or absence of anti-tumor immune cells from the tumor microenvironment, will guide us in improving existing immunotherapeutic therapies or develop novel combination therapies.