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Clin Cancer Res. 2015 May 15;21(10):2256-62. doi: 10.1158/1078-0432.CCR-14-2959.

Immune checkpoint modulation for non-small cell lung cancer.

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Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Université Paris Sud-XI, Faculté de Médecine, Le Kremlin Bicêtre, Paris, France.
Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.


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.

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