Researcher Database
Dr. Lisa Sevenich
Paul-Ehrlich-Str.42-44
60596 Frankfurt
Programs
Radiation Oncology and Imaging (ROI)
Cancer Immunotherapy (CI)
Summary
Tumor microenvironment targeted therapies against brain metastasis
The brain has long been regarded as an immunologically sanctuary site in which the blood-brain barrier restricts the entry of blood-borne immune cells. Hence, CNS cancers are regarded as immunologically cold tumors that poorly respond to immunotherapy. However, the actual extent of infiltration of blood-borne immune cells into the brain in CNS cancers remained elusive for a long time. Recent insight indicates that primary and metastatic brain cancers induce significant recruitment of blood-borne cells from the lymphoid and myeloid lineage that together with brain-resident cells form a highly complex and dynamic microenvironment.
Our research aims at dissecting the cellular and molecular identity of brain metastasis-associated immune cells in different tumor entities that frequently metastasize to the brain (i.e. melanoma, breast- and lung cancer). A particular focus is put on effects of radiotherapy as a critical modulator of brain metastasis-associated inflammation. We employ a comprehensive set of experimental models and patient specimen to gain detailed insight into the immune landscape of brain metastasis. Our goal is to understand the genetic imprinting of immune cells within the brain metastasis microenvironment and to study the impact of standard therapy on tumor-associated inflammation to identify novel therapeutic avenues to sensitize brain metastasis towards immunotherapy.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.