Group Schenk

The incidence of cancer is steadily rising and presents a major public health problem in many parts of the world. A key player in preventing and controlling malignant disease is the immune system. Unfortunately, in many cancer patients anti-tumor immunity is diminished. This malfunction can be caused by improper maturation of dendritic cells (DC), which thus cannot prime and activate cells of the adaptive immune system, in particular CD8+ T lymphocytes. Cytotoxic CD8+ T lymphocytes (CTL) are essential for killing tumor cells. Using tumor-immunotherapy we aim to enhance the function of the immune system to battle cancer. Specifically, our research group aims to investigate mechanisms to induce DC that can cross-present tumor specific antigens and induce an effective anti-tumor CTL response.



Current research projects

Dendritic cells and their co-stimulatory properties for cytotoxic T cells in melanoma

Group Schenk The activation of an effective adaptive anti-tumor response relies mainly on presentation of tumor antigens and stimulation by DC. Despite extensive research, the phenotypes and functions of tumor-infiltrating DC (TIDC) remain largely elusive and cross-presentation of tumor antigen is not well understood. We are elucidating the phenotypes and functions of TIDC and how to manipulate them both in vitro and in vivo to induce a tumor- specific CTL response in melanoma. Thereby, we aim to identify ways to reprogram TIDC to present tumor antigens and activate an adaptive immune response against melanoma.

Generation of potent cross-presenting Dendritic Cells (DC) for tumor immunotherapy

Group Schenk Only specific subsets of DC are able to present tumor antigens to CD8+ T cells in a process called cross-presentation. We aim to elucidate the mechanism(s) of cross-presentation and how this process can be manipulated in melanoma. Therefore, we are establishing models to test human monocyte derived DC as well as mouse bone marrow derived DC (BM-DC) for their ability to cross-present antigen. The knowledge of how cross-presentation is regulated in vitro may allow us to manipulate this process in vivo. Treated BM-derived DC will be tested in adoptive transfer experiments as prophylactic and therapeutic treatment for established melanoma. Together, these data should identify ways to promote frequency and enhance function of cross-presenting DC and to contribute to anti-tumor response.

Cross-presentation by Dendritic Cells: Different pathways of antigen processing and transport leading to presentation of exogenous antigen on MHC class I to CD8+ T cells

Highly multiplex, spatially resolved immunophenotyping of PDAC for biomarker discovery

Group Schenk The tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC) is diverse, comprising various cell types that may either enhance or attenuate tumor immunity and disease progression, as well as response to therapies. It is therefore essential to dissect the immunological landscape in human PDAC tissues and to assess the correlation of various cell subsets and tumor-derived immunosuppressive factors to patient survival and other clinical parameters. Utilizing a novel approach to perform spatially resolved multiplex immunohistochemistry, we intend to delineate the phenotypes of tumor-infiltrating immune subpopulations in exquisite detail. Integrating these findings with transcriptomic data and tumor genotype signatures will allow us to unravel the mechanistic and prognostic relevance of certain immune markers in PDAC.

25-plex imaging mass cytometry (IMC) image of a human PDAC tissue section shown in four images with 6 markers each. Overview (top), zoom (bottom)