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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.

Author information

1
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.
2
Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France.
3
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
4
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.

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.

PMID:
25979932
DOI:
10.1158/1078-0432.CCR-14-2959
[Indexed for MEDLINE]
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