title: Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer.
abstract: BACKGROUND
  Studies suggest that tumour-infiltrating lymphocytes (TILs) and inflammation markers have independent roles in non-small cell lung cancer (NSCLC), but the relationship between the two pronostic factors remains unclear. In this study, we investigated TILs and inflammation markers in with patients advanced stage NSCLC and assessed the association of their levels with prognosis.
  
  
  METHODS
  TILs were evaluated by immunohistochemical staining for cluster of differentiation 3 (CD3) and cluster of differentiation 5 (CD5) and by hematoxylin and eosin staining for non-specific lymphocyte. We investigated the localisation pattern of TILs in advanced stage NSCLC. We divided all cases into two groups: TILs-high and TILs-low groups, by 75th percentile of the population of. In our study, inflammation markers were assessed by C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR).
  
  
  RESULTS
  The results showed that the presence of intra-tumoral high CD3+and low CD5+were an independent prognostic factor for overall survival (respectively, P = 0.022 and P = 0.025). Moreover, the high NLR and serum high CRP levels were associated with poor survival (respectively, P = 0.008; P = 0.027). In multi-variate survival analysis, the high CD3+, low CD5+, high NLR, tumour node metastasis (TNM) stage, depth of tumour invasion and lymph node metastasis remained independent prognostic factors (respectively, P = 0.018, P = 0.020, P = 0.024, P = 0.038, P = 0.020 and P = 0.047).The high NLR was detected negative correlation with intra-tumoral CD3+and positive correlation with intra-tumoral CD5+(respectively, r = -0.623, P = 0.012; r = 0.628, P = 0.028).
  
  
  CONCLUSIONS
  This study is first report demonstrating the prognostic value of intra-tumoral low CD5+with NSCLC. Increased CD3+and low CD5+was observed in patients with poor prognosis; the two molecules were correlated with NLR, suggesting that inflammation might be used as improve therapeutic efficacy to immunotherapy for advanced NSCLC.
authors.affiliation: Department of Chest Diseases, Suleyman Demirel University of Medicine, Isparta, Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Dirican
authors.affiliation: Department of Pathology, Isparta State Hospital, Isparta, Turkey.
authors.forename: Yeliz Arman
authors.initials: YA
authors.lastname: Karakaya
authors.affiliation: Department of Thoracic Surgery, Isparta State Hospital, Isparta, Turkey.
authors.forename: Sedat
authors.initials: S
authors.lastname: Gunes
authors.affiliation: Department of Pathology, Mersin University of Medicine, Isparta, Turkey.
authors.forename: Ferah Tuncel
authors.initials: FT
authors.lastname: Daloglu
authors.affiliation: Department of Medical Oncology, Celal Bayar University Faculty of Medicine, Manisa, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dirican
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D018956:CD5 Antigens; D002097:C-Reactive Protein
keywords: NLR; NSCLC; TIL; prognosis