Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer

PLoS One. 2014 Sep 19;9(9):e106914. doi: 10.1371/journal.pone.0106914. eCollection 2014.

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).

Methods and findings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Karnofsky Performance Status
  • Multivariate Analysis
  • Neoplasm Grading
  • Nutritional Status*
  • Prealbumin / metabolism*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Tumor Microenvironment*

Substances

  • Prealbumin
  • C-Reactive Protein

Grant support

This work was supported by 1. Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Descartes, Université Pierre et Marie Curie, Labex Immunooncology (11LAXE62_9UMRS872 FRIDMAN). Authors who received the funding: DD, IC, MCDN www.sorbonne-paris-cite.fr. 2. Fondation ARC pour la Recherche sur le Cancer (SL220110603483). Author who received the funding: IC www.fondation-arc.org. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.