Systemic Inflammation, Nutritional Status and Tumor Immune Microenvironment Determine Outcome of Resected Non-Small Cell Lung Cancer

• Published in: PloS one Vol. 9; no. 9; p. e106914
• Main Authors: Alifano, Marco, Mansuet-Lupo, Audrey, Lococo, Filippo, Roche, Nicolas, Bobbio, Antonio, Canny, Emelyne, Schussler, Olivier, Dermine, Hervé, Régnard, Jean-François, Burroni, Barbara, Goc, Jérémy, Biton, Jérôme, Ouakrim, Hanane, Cremer, Isabelle, Dieu-Nosjean, Marie-Caroline, Damotte, Diane
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.09.2014; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Analysis; C-reactive protein; C-Reactive Protein - metabolism; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Care and treatment; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell survival; Chemotherapy; Chronic obstructive pulmonary disease; Cytokines; Dendritic cells; Determinants; Human health and pathology; Infiltration; Inflammation; Karnofsky Performance Status; Laboratories; Life Sciences; Lung cancer; Lung diseases; Lymphocytes; Medical prognosis; Medicine and Health Sciences; Metastases; Metastasis; Multivariate Analysis; Neoplasm Grading; Non-small cell lung cancer; Non-small cell lung carcinoma; Nutrition; Nutritional Status; Pathology; Patients; Prealbumin - metabolism; Prognosis; Radiation therapy; Retrospective Studies; Risk analysis; Statistical analysis; Studies; Surgery; Survival; Survival Analysis; Thoracic surgery; Tumor Microenvironment; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106914

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). 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. Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.