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

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

G Alì  1 , L Boldrini, M Lucchi, A Picchi, M Dell'Omodarme, M C Prati, A Mussi, V Corsi, G Fontanini
Affiliations

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

G Alì et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Immunohistochemical staining for tryptase-positive mast cells (A), Foxp3-positive lymphocytes (B), CD8-positive lymphocytes (C), and microvessel count (D) in mesotheliomas. Original magnification, × 100.
Figure 2
Figure 2
Kaplan–Meier overall survival (A) and time to progression (B) curves for tryptase MCs counts divided into two groups above and below the median value; Kaplan–Meier overall survival (C) and time to progression (D) curves for Foxp3 counts divided into two groups above and below the median value; (E) Kaplan–Meier overall survival curves for combination of tryptase MCs and Foxp3 counts.
See this image and copyright information in PMC

References

    1. Ahmadzadeh M, Rosenberg SA (2006) IL-2 administration increases CD4+ CD25+ Foxp3+ regulatory T cells in cancer patients. Blood 107: 2409–2414 - PMC - PubMed
    1. Akbar AN, Borthwick NJ, Wickremasinghe RG, Panayoitidis P, Pilling D, Bofill M, Krajewski S, Reed JC, Salmon M (1996) Interleukin-2 receptor common gamma-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: selective induction of anti-apoptotic (bcl-2, bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene expression. Eur J Immunol 26: 294–299 - PubMed
    1. Alì G, Boldrini L, Lucchi M, Mussi A, Corsi V, Fontanini G (2009) Tryptase mast cells in malignant pleural mesothelioma as an independent favorable prognostic factor. J Thorac Oncol 4: 348–354 - PubMed
    1. Anraku M, Cunningham KS, Yun Z, Tsao MS, Zhang L, Keshavjee S, Johnston MR, de Perrot M (2008) Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 135: 823–829 - PubMed
    1. Armstrong AC, Eaton D, Ewing JC (2001) Science, medicine, and the future: cellular immunotherapy for cancer. BMJ 323: 1289–1293 - PMC - PubMed

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