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

Our plain-English summary of Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact, by G. Alì, L. Boldrini, M. Lucchi, et al (British Journal of Cancer, 2009).

The study

• Authors: G. Alì, L. Boldrini, M. Lucchi, A. Picchi, M. Dell'Omodarme, M.C. Prati, A. Mussi, V. Corsi, G. Fontanini
• Journal: British Journal of Cancer
• Published: 2009;101(11):1869-75
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This study examined tumour tissue from 93 patients with malignant pleural mesothelioma who had surgery at the University of Pisa, Italy, between January 1999 and May 2008. Sixty had received interleukin-2 (IL-2), an immune-stimulating drug, into the chest cavity before surgery. The other 33 had no treatment before surgery. The article did not report asbestos exposure. Pathologists stained the tissue to count immune cells (mast cells and lymphocyte types) and small blood vessels, and to measure a growth factor, VEGF. Compared with untreated patients, the treated group had more tryptase mast cells, CD8 lymphocytes and Foxp3 lymphocytes, and fewer microvessels. Differences in CD4 lymphocytes, chymase mast cells and VEGF were not statistically significant. Among treated patients, higher tryptase mast cell counts were associated with longer survival and time to progression. Higher Foxp3 counts were associated with shorter survival and time to progression. Both counts remained independent predictors of overall survival after accounting for gender, age, histology, performance status and stage. Combining the two counts separated patients into groups with different survival. The authors concluded that these two counts may predict outcome in IL-2-treated patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Comparison of two series of surgical patients (IL-2-treated vs untreated) using immunohistochemistry on tumour specimens, with survival analysis in the IL-2-treated group
• Who was studied: 93 patients with malignant pleural mesothelioma who had surgical resection at the Department of Cardio-Thoracic Surgery, University of Pisa, Italy, January 1999 to May 2008: 60 treated with IL-2 before surgery and 33 untreated
• Exposure: Preoperative intra-pleural interleukin-2 (given every other day three times before surgery) compared with no preoperative treatment. Asbestos exposure is not reported.
• Main results:
  • Tryptase-positive mast cells were higher in the IL-2-treated group than in the untreated group (mean 26.18 vs 19.32; P = 0.04)
  • CD8 lymphocytes (mean 90.83 vs 67.11; P = 0.004) and Foxp3 lymphocytes (mean 11.80 vs 6.12; P = 0.02) were significantly higher in the IL-2-treated group than in the untreated group
  • CD4 lymphocytes were higher in the IL-2-treated group, but the difference was not statistically significant (P = 0.13)
  • Microvessel count (CD34) was significantly lower in the IL-2-treated group than in the untreated group (mean 62.12 vs 147.70; P = 0.0001)
  • No difference was found between the groups in chymase-positive mast cells (P = 0.60)
  • No difference was found between the groups in the percentage of VEGF-positive tumour cells (P = 0.64)
  • Across both groups' clinical features, microvessel count was associated with histologic subtype (P = 0.0047), higher in sarcomatoid and biphasic than in epithelioid tumours
  • In IL-2-treated patients, the sarcomatoid subtype was associated with worse overall survival (P = 0.02) and shorter time to progression (P = 0.02)
  • In IL-2-treated patients, a higher tryptase-positive mast cell count (split at the median) was associated with better overall survival (P = 0.02) and longer time to progression (P = 0.01)
  • In IL-2-treated patients, a higher Foxp3 (regulatory T cell) count (split at the median) was associated with worse overall survival (P = 0.000002) and shorter time to progression (P = 0.0039)
  • In multivariate analysis of overall survival in IL-2-treated patients, tryptase mast cell and Foxp3 counts both remained independent predictors. No adjusted analysis of time to progression was reported.
  • Combining the two counts split IL-2-treated patients into three groups with significantly different overall survival (P = 0.00000017). Group III (low Foxp3, high tryptase; n = 15) had better survival than group II (both high or both low; n = 27) and group I (high Foxp3, low tryptase; n = 14).
• The authors' conclusion: The authors concluded that intra-pleural IL-2 led to increases in tryptase-positive mast cells and in CD8 and Foxp3 lymphocytes, along with reduced tumour vascularity. They proposed that tryptase-positive mast cell and regulatory T cell counts may be strong predictors of outcome in mesothelioma patients treated with IL-2.
• Limitations the authors state:
  • The authors stated that further studies are needed to confirm the functional properties of the effector and regulatory immune cells

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Angiogenesis, Tumor-Infiltrating Lymphocytes, Immunohistochemistry, Mesothelioma.

Related studies

• Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? — M. Lucchi, A. Picchi, et al. (2010)
• A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma — C.W. Mulatero, R.T. Penson, et al. (2001)
• Progress report on the palliative therapy of 100 patients with neoplastic effusions by intracavitary low-dose interleukin-2 — P. Lissoni, M. Mandalà, et al. (2001)
• Enhanced interleukin activity following asbestos inhalation — D.P. Hartmann, M.M. Georgian, et al. (1984)
• Safety, feasibility and therapeutic activity of intrapleural autologous lymphocyte conditioned medium followed by systemic recombinant interleukin-2 and interferon-alpha in a patient with malignant pleural mesothelioma — S. Duensing, H. Hamm, et al. (1997)
• Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study — S.H. Goey, A.M. Eggermont, et al. (1995)

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