title: Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer.
abstract: BACKGROUND
  Treatments of non-small-cell lung cancer (NSCLC)-particularly of the squamous subtype-are limited. In this article, we describe the immunomodulatory environment in NSCLC and the potential for therapeutic targeting of the immune system through cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) immune-checkpoint pathway blockade.
  
  
  METHODS
  We searched PubMed and presented abstracts for publications describing the clinical benefit of checkpoint blockade in NSCLC.
  
  
  RESULTS
  Antibody-mediated checkpoint molecule blockade is being investigated in NSCLC, and of these approaches, the anti-CTLA-4 antibody ipilimumab has undergone the most extensive clinical study. By targeting the immune system rather than specific antigens, checkpoint blockade agents differ from vaccine therapy. In a phase II study in advanced NSCLC, phased ipilimumab with chemotherapy demonstrated the greatest efficacy in squamous NSCLC. A phase I study of nivolumab, an anti-PD-1 antibody, has suggested that this agent is also active against squamous and non-squamous NSCLC. Ongoing phase III studies are evaluating the therapeutic potential of these agents.
  
  
  CONCLUSIONS
  Although treatment options for NSCLC are limited, a better understanding of the immune profile of this disease has facilitated the development of immunotherapeutics that target checkpoint blockade molecules, and clinical evaluation to date supports combining checkpoint blockade with chemotherapy for squamous NSCLC.
authors: Central European Cooperative Oncology Group (CECOG), Vienna, Vienna General Hospital, Vienna, Austria. christoph.zielinski@meduniwien.ac.at
authors: C
authors: C
authors: Zielinski
authors: S
authors: S
authors: Knapp
authors: C
authors: C
authors: Mascaux
authors: F
authors: F
authors: Hirsch
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
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