tailieunhanh - Ebook Fast facts - Non-small-cell lung cancer: Part 2

Part 2 book “Fast facts - Non-small-cell lung cancer” has contents: Immuno-oncology, first and second-line chemotherapy in advanced NSCLC, management of brain metastases, personalized treatment in advanced NSCLC. | 5 Immuno-oncology Rajiv Kumar FRACP MBChB BMedSc, The Royal Marsden NHS Foundation Trust, London, UK; and Jordi Remon MD, Medical Oncology Department, Gustave Roussy, Villejuif, France In general, non-small-cell lung cancer (NSCLC) is associated with tumor DNA damage and mutations induced by carcinogens in tobacco smoke. In the mid-1990s an antibody to one of the murine immune checkpoints was found to cure tumors in The first antibody to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was licensed 15 years later for the treatment of melanoma. This reignited the pursuit of immunotherapies in the management of cancer, including Known as immune checkpoint inhibitors, these therapies target the programmed cell death 1 (PD-1) receptor, programmed cell death ligand-1 (PD-L1) and the CTLA-4 receptor. Mechanism of action PD-1 is an inhibitory cell-surface receptor that is expressed on activated T cells, B cells, natural killer cells, monocytes and dendritic cells. The effector function of T cells that express PD-1 in the tumor microenvironment can be suppressed when PD-1 is coupled to the ligand PD-L1 (B7-H1) or PD-L2 (B7-DC) on tumor cells, thus preventing an immune attack on the The PD-L1 and PD-L2 ligands cross-compete for PD-1 binding; although PD-L2 has a sixfold higher binding affinity for PD-1, it has lower levels of expression, so that PD-L1 is the best ligand to target. Inhibition of the PD-1/PD-L1 immune checkpoint using monoclonal antibodies (mAbs) prevents the inhibition of the effector T-cell function, allowing T cells to maintain their tumor cell killing function (Figure ).4 Drugs in development Several drugs are in development (Table ). The PD-1 inhibitors are immunoglobulin (Ig)G4 isotypes, while the PD-L1 inhibitors are IgG1 isotypes and are able to bind C1q and activate the complement © 2016 Health Press Ltd. 41 Fast Facts: Non-Small-Cell Lung Cancer T cell receptor Antigen T .