title: Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment.
abstract: Cancer immunotherapy has been a subject of intense research over the last several years, leading to new approaches for modulation of the immune system to treat malignancies. Immune checkpoint inhibitors (anti-CLTA-4 antibodies and anti-PD-1/PD-L1 antibodies) potentiate the host's own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non-small cell lung cancer (NSCLC)-all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases.
authors.affiliation: From the German Cancer Research Center, University of Heidelberg, Heidelberg, Germany; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna CNS Unit, Vienna, Austria; Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: From the German Cancer Research Center, University of Heidelberg, Heidelberg, Germany; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna CNS Unit, Vienna, Austria; Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Vyshak A
authors.initials: VA
authors.lastname: Venur
authors.affiliation: From the German Cancer Research Center, University of Heidelberg, Heidelberg, Germany; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna CNS Unit, Vienna, Austria; Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: From the German Cancer Research Center, University of Heidelberg, Heidelberg, Germany; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center Vienna CNS Unit, Vienna, Austria; Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA; Burkhardt Brain Tumor and Neuro-Oncology Center, Neurologic Institute, Cleveland Clinic, Cleveland, OH; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000556:secondary; D060908:CTLA-4 Antigen / Q000276:immunology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000276:immunology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor