title: Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer.
abstract: BACKGROUND
  The role of the interaction between tumor cells and inflammatory cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the authors assessed the prognostic impact of intratumoral cluster of differentiation 66b (carcinoembryonic antigen-related cell adhesion molecule 8 [CD66b])-positive neutrophils and of the intratumoral CD66b-positive neutrophil-to-cluster of differentiation 8 (cell surface antigen T8 [CD8])-positive lymphocytes (the CD66b-positive neutrophil-to-CD8-positive lymphocyte ratio [iNTR]) in patients with resectable NSCLC.
  
  
  METHODS
  Expression levels of CD66b and CD8 were evaluated by immunohistochemistry on tissue microarrays consisting of 632 NSCLC specimens from patients who underwent curative surgery. The relation between clinicopathologic variables and patient outcome was assessed.
  
  
  RESULTS
  Intratumoral CD66b-positive neutrophils were elevated in 318 patients (50%). In univariate analysis, an increase in CD66b-positive cells was associated with a high cumulative incidence of relapse (CIR) (median CIR, 51 months for low CD66b-positive cell density; 36 months for high CD66b-positive cell density; P = .002) and trended toward worse overall survival (OS) (median OS, 57 months for low CD66b-positive cell density; 54 months for high CD66b-positive cell density; P = .088). The iNTR was elevated in 190 patients (30%). An increased iNTR was strongly associated with both a high CIR (median CIR: 43 months for an iNTR ≤1; 34 months for an iNTR >1; P < .0001) and poor OS (median OS: 60 months for an iNTR ≤1; 46 months for an iNTR >1; P < .0001). In multivariate analysis, independent prognostic factors for a higher CIR were high iNTR (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56-0.90; P = .005) and tumor stage >I, (HR, 0.39; 95% CI, 0.30-0.52; P < .0001). Independent prognostic factors for worse OS were a high iNTR (HR, 0.70; 95% CI, 0.54-0.91; P = .007) and tumor stage >I (HR, 0.35; 95% CI, 0.26-0.47; P < .0001).
  
  
  CONCLUSIONS
  The current results indicated that the iNTR is a novel, independent prognostic factor for a high rate of disease recurrence and poor OS in patients with resectable NSCLC.
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, University Hospital Center of Nice, Nice, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Cécile
authors.initials: C
authors.lastname: Ortholan
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: Céline
authors.initials: C
authors.lastname: Coëlle
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mouroux
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins