title: Predictive biomarkers for programmed death-1/programmed death ligand immune checkpoint inhibitors in nonsmall cell lung cancer.
abstract: OBJECTIVE
  Immune checkpoint inhibitors, antiprogrammed death receptor 1 (anti-PD-1)/antiprogrammed death-ligand 1 (anti-PD-L1), are new therapeutic regimens for managing advanced nonsmall cell lung cancer patients, giving an overall response rate of approximately 20% as monotherapy in second-line treatment. The use of predictive biomarkers for identifying patients suitable for these therapies is an important issue not only for making treatment decisions, but also from a medical economic point of view.
  
  
  RESULTS
  Among potential predictive biomarker candidates for anti-PD-1/PD-L1 treatments in nonsmall cell lung cancer, the expression of PD-L1 (as determined by immunohistochemistry) is currently the most studied. PD-L1 positivity has been associated with higher response rate to anti-PD-1/PD-L1 therapies. However, several observations suggest that the predictive value of PD-L1 expression is not clear-cut. We review other potential predictive biomarkers, including programmed death-ligand 2, IFN-γ, and genetic signatures.
  
  
  CONCLUSIONS
  Standardized techniques and conditions for evaluating PD-L1 expression (tissue quality and age, percentage positivity threshold, managing heterogeneous and dynamic expression) are critical for establishing the use of this protein as a predictive marker. Care should be also taken when using anti-PD-1/PD-L1 therapies in combination with other therapies, which may impact the predictive value of PD-L1 expression.
authors.affiliation: aMedical Oncology DepartmentbLaboratoire d'immunomonitoring en Oncologie UMS 3655 CNRS/US 23 INSERM, Gustave Roussy, Villejuif, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Remon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: David
authors.initials: D
authors.lastname: Planchard
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma