Group Leader: Immune biology of MSI cancer @ Heidelberg University Hospital and DKFZ
Heidelberg, GermanyKeywords (click a keyword to view other similar labs): theoretical • experimental • tumor evolution • DNA mismatch repair system • microsatellite instability • inherited cancer syndrome • Lynch syndrome • colorectal cancer • carcinogenic pathways • tumor phylogeny • immune surveillance • immunoediting • cancer risk • mutational landscape • immune evasion • cancer neoantigens • cancer vaccines.
Description: The MSI Cancer Group at the Department of Applied Tumor Biology (ATB) focuses on the pathogenesis and immune biology of cancers with the molecular phenotype of mismatch repair deficiency. Due to the defective DNA mismatch repair, these tumors accumulate extremely high numbers of mutations (microsatellite instability, MSI), which due to the Darwinian selection process are shared among different MSI tumors. The unique feature of MSI cancer evolution is that mutations conferring growth advantage at the same time result in the generation of novel, highly immunogenic cancer neoantigens. Thus, MSI cancer evolution is governed by (1) the proliferative advantage of cancer cells acquired through mutations and (2) the relevance of the neoantigens contributing to cancer cell elimination by the immune system. We have pioneered research on the immune biology of MSI cancers, identified relevant mutational and immunological targets arising during MSI cancer evolution and prepared the first-in-human vaccine against these cancers. This opened the possibility of tumor-preventive vaccines for Lynch syndrome carriers who have an inherited predisposition to develop cancer at a young age. In collaboration with EMCL Heidelberg, we now focus on developing mathematical models reflecting MSI cancer evolution and simulating the effect of immune-modulatory approaches in order to design optimal immune prevention strategies for Lynch syndrome carriers and interventions for patients with MSI cancer.