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

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 þ 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 þ lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression.

Effect of Rapamycin and Interleukin-2 on Regulatory CD4+CD25+Foxp3+ T Cells in Mice After Allogenic Corneal Transplantation

“…31 A recent study reported that IL-2 treatment lead to a reduced angiogenesis in subjects with malignant pleural mesothelioma. 32 Moreover, the aqueous humor level of IL-2 was significantly lower in patients with recurrent choroidal neovascularization and macular edema. 33 These findings indicated the antiangiogenetic effect of IL-2.…”

Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma

“…While phase II intrapleural IL-2 has demonstrated some effectiveness in treating MPM, other routes of administration (intravenous and/or subcutaneous) as first-line treatment have failed to do so [114,115]. In a group of 60 MPM patients who received pre-operative intrapleural IL-2 treatment, a significantly higher number of T regs was observed in surgical specimens, as compared to 33 patients who did not receive IL-2 [116]. Within the IL-2-treated group, high T regs , defined as greater than the median on immunohistochemical assessment, was correlated with both decreased patient survival and increased tumor recurrence on subgroup analysis.…”

Increased frequency of circulating invariant natural killer T cells in malignant pleural mesothelioma patients

“…45 Histological findings were reviewed treatment. [14][15][16][17] Several studies have also been performed with interferons (IFN) (α, β and γ), and in particular, it has been demonstrated that patients treated with IFNβ have an increased survival, based on the dual action of interferon on both immune and tumor cells. 18 In addition, new and potentially effective treatments have been reported with either the active, where one or several antigens are used for triggering an immune response, or the passive immunotherapy, which relies on effector cells, isolated and activated in vitro before their re-injection in vivo.…”