title: Non-Small Cell Lung Cancer, PD-L1, and the Pathologist.
abstract: BACKGROUND
  Although most primary cancers of the lung carry a heavy mutational load and will potentially present many "nonself" antigens to the immune system, there are a wide range of possible mechanisms for tumors to avoid so-called immune surveillance. One such mechanism is the adoption of immune checkpoints to inhibit the host immune response. Immune checkpoint inhibitors show great promise in the treatment of advanced non-small cell lung cancer.
  
  
  OBJECTIVE
  To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti-PD-1 or anti-PD-L1 therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges.
  
  
  METHODS
  Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used.
  
  
  CONCLUSIONS
  The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead.
authors.affiliation: From the Department of Pathology, Aberdeen University School of Medicine (Dr Kerr), and the Department of Oncology (Dr Nicolson), Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kerr
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Nicolson
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007157:Immunologic Surveillance / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000639:trends; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D015507:Drugs, Investigational; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor