Main Field(s) of Research, Abstract
Our research group studies the interaction between the immune system and cancer. We follow an iterative approach, such that we are inspired by clinical observations or problems, address selected topics using mouse models and validate our findings using samples from cancer patients. Our laboratory has a strong expertise in fundamental research as well as in translational aspects.
It is well accepted now that the immune system plays an important role in preventing cancer. This is illustrated by the occurrence of tumor-specific immunity in cancer patients and by the higher incidence of cancer in immunosuppressed individuals. There is increasing evidence that immune cells and tumor cells influence each other and consequently, the process of immunosurveillance is thought to exist in three phases: elimination, equilibrium and escape. The elimination phase is characterized by the recognition and the elimination of transformed cells by the immune system. Successful completion of this step prevents progression to subsequent phases. During the equilibrium phase the immune system keeps the malignant cells under control but does not eliminate them. Tumor escape occurs when cancer cells evade immunological control by developing tumor-intrinsic and -extrinsic strategies, resulting in clinically detectable disease.
The first requisite to develop an antitumor immune response is the capture of tumor-associated antigens (TAAs) by dendritic cells (DCs) that subsequently migrate to the draining lymph node to interact with naïve, tumor-specific T cells. DCs are special antigen-presenting cells (APCs) present in all tissues, which capture and process antigens for presentation on MHC class II and crosspresentation on MHC class I molecules. For the induction of protective immunity DCs have to undergo a process of maturation, which results from innate stimuli. In the absence such signals, however, the presentation of antigens by DCs results in peripheral T cell tolerance or to the induction regulatory T cells (Treg). The final major step in the antitumor immunity process consists in the migration of activated, tumor-specific T cells from the draining lymph node to the tumor site.
Because most TAAs are presumably not presented in association with strong innate stimuli and because the tumor developed different strategies of immune suppression, the antitumor immune response is often compromised. Tumor-intrinsic mechanisms include the enhanced resistance to apoptosis through changes in the expression of molecules involved in apoptosis-signaling, the down-regulation of tumor associated antigens and antigen-presenting major histocompatibility complex (MHC) molecules or the down-regulation of other components involved in antigenpresentation and/or -processing. In addition, the tumor creates a highly immunosuppressive environment. Tumor-extrinsic mechanisms include the induction of central and/or peripheral tolerance of T cells to tumor specific antigens.
Our research aims to better understand mechanisms that preclude protective immunity against cancer in order to improve cancer therapy.
Main Fields of Research, Keywords
Clinical research; Human tumorimmunology; Animal models for cancer; Transgenic mice; Mouse tumorimmunology
Special Techniques and Equipment
Animal experiments; Cell culture; FACS analysis; Molecular biology; Standard immunological techniques and assays (human and mouse)
Education and Training
We have training opportunities for PhD students, PostDocs and medical dissertations.