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.