Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors

Mol Neurobiol. 2018 Aug;55(8):7072-7078. doi: 10.1007/s12035-018-0905-3. Epub 2018 Jan 30.

Abstract

Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

Keywords: Brain metastasis; Immune checkpoint inhibitors; Ipilimumab; Pembrolizumab.

Publication types

  • Review

MeSH terms

  • Antibodies / therapeutic use
  • Brain Neoplasms / immunology
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Humans
  • Immunotherapy*

Substances

  • Antibodies