title: Immune checkpoint modulation for non-small cell lung cancer.
abstract: Therapies targeting immune checkpoints have recently shown encouraging activity in patients with heavily pretreated advanced non-small cell lung cancer (NSCLC), independently of NSCLC histology or mutational status, with low toxicity profiles when used as monotherapy. Objective response rates of approximately 20% have been reported in patients with advanced NSCLC treated with antagonist antibodies targeting the immune checkpoint, programmed death 1 (PD-1) on activated T cells, or its primary ligand, programmed death ligand 1 (PD-L1) expressed within the tumor microenvironment. Response rates appear to be higher in patients with tumor PD-L1 expression documented by immunohistochemistry, although responses have been appreciated in patients with reportedly PD-L1-negative tumor specimens. Antibodies directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), another immunosuppressive T-cell signaling molecule, are also being evaluated in clinical trials, with one randomized phase II trial demonstrating improved immune-related progression-free survival in lung cancer patients when added to standard chemotherapy. Additional clinical trials are combining anti-CTLA-4 antibodies with either anti-PD-1 or anti-PD-L1 antibodies. Combinations of other immune checkpoint antagonists or agonist antibodies with anti-PD-1 or anti-PD-L1 antibodies are also being pursued.
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Université Paris Sud-XI, Faculté de Médecine, Le Kremlin Bicêtre, Paris, France. Jean-Charles.Soria@gustaveroussy.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Scott
authors.initials: S
authors.lastname: Gettinger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007155:Immunologic Factors