title: The inflammatory microenvironment in brain metastases: potential treatment target?
abstract: Brain metastases (BM) are frequent in cancer patients and are associated with high morbidity and mortality. The incidence of BM is increasing and only limited treatment strategies are available. Immunomodulatory agents are emerging as effective cancer therapeutics and a deeper understanding of the inflammatory microenvironment in BM might reveal new treatment possibilities. Although the brain has long been considered an 'immune-privileged' organ with limited capacity for inflammatory response, BM do contain tumor infiltrating lymphocytes (TILs). Moreover, dense infiltration with TIL showed an association with favorable patients' overall survival times. Microglia/macrophages were shown to be involved in the pivotal steps of BM formation by providing a "pre-metastatic niche" attracting BM initiating cells and to promote growth and survival of tumor cells in the CNS microenvironment. The anti-cytotoxic T lymphocyte antigen 4 (CTLA4) immune checkpoint inhibitor ipilimumab showed activity against melanoma BM in a clinical trial, thus providing proof of concept for effective therapeutic immunomodulation in patients with CNS metastases. Collectively, the available data show that BM harbors an active inflammatory microenvironment that may be exploited as treatment target.
authors.affiliation: Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center, CNS Tumors Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Central, Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Matthias.preusser@meduniwien.ac.at.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D002450:Cell Communication / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents
keywords: Brain metastases (BM); checkpoint inhibitor; inflammatory microenviroment; tumor infiltrating lymphocyte (TIL)