title: Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.
abstract: BACKGROUND
  Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC).
  
  
  RESULTS
  Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p<0.05). In multivariate analysis, prealbumin levels (Relative Risk (RR): 0.34 [0.16-0.73], p = 0.0056), CD8+ cell count in tumor tissue (RR = 0.37 [0.16-0.83], p = 0.0162), and disease stage (RR 1.73 [1.03-2.89]; 2.99[1.07-8.37], p = 0.0374- stage I vs II vs III-IV) were independent prognostic markers. When taken together, parameters related to systemic inflammation, nutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced.
  
  
  CONCLUSIONS
  Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.
authors.affiliation: Deparment of Thoracic Surgery, Paris Centre University Hospitals, AP-HP, Paris, France; University Paris Descartes; Paris, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.affiliation: University Paris Descartes; Paris, France; Deparments of Pathology, Paris Centre University Hospitals, AP-HP, Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mansuet-Lupo
authors.affiliation: Unit of thoracic Surgery, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Lococo
authors.affiliation: University Paris Descartes; Paris, France; Departments of Chest Disease, Paris Centre University Hospitals, AP-HP, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roche
authors.affiliation: Deparment of Thoracic Surgery, Paris Centre University Hospitals, AP-HP, Paris, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bobbio
authors.affiliation: Deparment of Thoracic Surgery, Paris Centre University Hospitals, AP-HP, Paris, France.
authors.forename: Emelyne
authors.initials: E
authors.lastname: Canny
authors.affiliation: Deparment of Thoracic Surgery, Paris Centre University Hospitals, AP-HP, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schussler
authors.affiliation: Unit of thoracic Surgery, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dermine
authors.affiliation: Deparment of Thoracic Surgery, Paris Centre University Hospitals, AP-HP, Paris, France; University Paris Descartes; Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Régnard
authors.affiliation: Deparments of Pathology, Paris Centre University Hospitals, AP-HP, Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burroni
authors.affiliation: University Paris Descartes; Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Goc
authors.affiliation: University Paris Descartes; Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Biton
authors.affiliation: University Paris Descartes; Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Hanane
authors.initials: H
authors.lastname: Ouakrim
authors.affiliation: University Paris Descartes; Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: University Paris Descartes; Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.affiliation: University Paris Descartes; Paris, France; Deparments of Pathology, Paris Centre University Hospitals, AP-HP, Paris, France; INSERM U1138, Cancer and Immune Escape, Cordeliers Research Center, Paris, France; University Pierre and Marie Curie, UMRS U1138, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D017567:Karnofsky Performance Status; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009752:Nutritional Status; D011228:Prealbumin / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D059016:Tumor Microenvironment
chemical_list: D011228:Prealbumin; D002097:C-Reactive Protein