Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact

Br J Cancer. 2009 Dec 1;101(11):1869-75. doi: 10.1038/sj.bjc.6605438.

Abstract

Background: Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value.

Methods: Tumour-infiltrating lymphocytes (CD4, CD8, Foxp3), mast cells (MCs) (tryptase and chymase), microvessel count (MVC) and VEGF were determined by immunohistochemistry in two series of MPM patients: 60 patients treated with intra-pleural preoperative IL-2 and 33 patients untreated.

Results: Tryptase MCs, and CD8 and Foxp3 lymphocytes were significantly increased in the IL-2-treated group, whereas MVC was significantly lower in the same group. Moreover, in the IL-2-treated group, greater tryptase+MCs and greater Foxp3 lymphocytes were associated with improved and poorer clinical outcomes, respectively. Notably, when these two immunological parameters were combined, they predicted outcomes more effectively.

Conclusions: This study showed that IL-2 treatment leads to a significant increase of immunological parameters, concomitantly with a reduction in vasculature, providing new insight into the cancer mechanisms mediated by IL-2. Moreover, these results suggest that tryptase-positive MCs and Foxp3+ lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression.

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immunohistochemistry
  • Interleukin-2 / immunology
  • Interleukin-2 / therapeutic use*
  • Lymphocytes / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Mast Cells / immunology
  • Mesothelioma / blood supply
  • Mesothelioma / drug therapy*
  • Mesothelioma / immunology
  • Mesothelioma / pathology
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / immunology
  • Pleural Neoplasms / blood supply
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / immunology
  • Pleural Neoplasms / pathology
  • Prognosis
  • Survival Rate
  • Treatment Outcome
  • Tryptases / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2
  • Tryptases