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British Journal of Cancer (2009) 101, 1869 1875& 2009 Cancer Research UK All rights reserved 0007 0920/09 $32.00
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Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact
G Al1, L Boldrini1, M Lucchi2, A Picchi2, M DellOmodarme3, MC Prati3, A Mussi2, V Corsi1 and G Fontanini*,1 1Division of Pathological Anatomy, Department of Surgery, University of Pisa, Via Roma 57, Pisa 56126, Italy; 2Division of Thoracic Surgery, Department of
Cardio-Thoracic Surgery, University of Pisa, Via Paradisa, Pisa 5614, Italy; 3Scuola Normale Superiore and Istituto di Fisica Nucleare, Section of Pisa, Pisa 56126, Italy
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.
British Journal of Cancer (2009) 101, 1869 1875. doi:http://dx.doi.org/10.1038/sj.bjc.6605438
Web End =10.1038/sj.bjc.6605438 http://www.bjcancer.com
Web End =www.bjcancer.com & 2009 Cancer Research UK
Keywords: malignant pleural mesothelioma; tumour microenvironment; interleukin-2; prognosis
TranslationalTherapeutics
Malignant pleural mesothelioma (MPM) is a relatively rare tumour with a growing occurrence in the past few decades throughout the world. It is a fatal neoplasm, with a median survival of 12 months in patients receiving palliative care (Robinson et al, 2005). Presently, there is no satisfactory...