Mesothelioma Research Today is a free monthly online journal that collates and summarizes the latest research about Mesothelioma, including details on asbestos, symptoms, treatment, causes.

Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma.

Anraku M, Cunningham KS, Yun Z, Tsao MS, Zhang L, Keshavjee S, Johnston MR, de Perrot M

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.

OBJECTIVE: The aim of the study was to determine the impact of tumor-infiltrating lymphocytes on survival in patients with malignant pleural mesothelioma treated with induction chemotherapy followed by extrapleural pneumonectomy. METHODS: We performed an immunohistochemical analysis of 32 extrapleural pneumonectomy specimens to assess the distribution of T-cell subtypes (CD3(+), CD4(+), and CD8(+)), regulatory subtypes (CD25(+) and FOXP3(+)), and memory subtype (CD45RO(+)) within the tumor. RESULTS: Patients with high levels of CD8(+) tumor-infiltrating lymphocytes demonstrated better survival than those with low levels (3-year survival: 83% vs 28%; P = .06). Moreover, high levels of CD8(+) tumor-infiltrating lymphocytes were associated with a lower incidence of mediastinal node disease (P = .004) and longer progression-free survival (P = .05). Higher levels of CD8(+) tumor-infiltrating lymphocytes were observed in patients treated with cisplatin and pemetrexed than in those treated with cisplatin and vinorelbine (P = .02). Patients presenting high levels of CD4(+) or CD25(+) tumor-infiltrating lymphocytes or low levels of CD45RO(+) also demonstrated a trend toward shorter survival. However, the presence of FOXP3(+) tumor-infiltrating lymphocytes did not affect survival. After multivariate adjustment, high levels of CD8(+) tumor-infiltrating lymphocytes remained an independent prognostic factor associated with delayed recurrence (hazard ratio = 0.38; confidence interval = 0.09-0.87; P = .02) and better survival (hazard ratio = 0.39; confidence interval = 0.09-0.89; P = .02). CONCLUSION: The presence of high levels of CD8(+) tumor-infiltrating lymphocytes is associated with better prognosis in patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma. The stimulation of CD8(+) lymphocytes can be a potential therapeutic strategy to improve outcome.

Published 31 March 2008 in J Thorac Cardiovasc Surg, 135(4): 823-9.
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Articles on Mesothelioma published 26 March 2008:

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors.   Thorax, 63(4): 345-51.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival <3 years; STS) and long term ... [Abstract] [Full-text]

Articles on Mesothelioma published 25 March 2008:

Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.   Cancer, 112(7): 1555-61.

BACKGROUND: Pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated ... [Abstract] [Full-text]

Articles on Mesothelioma published 21 March 2008:

Risk factors for major complications after extrapleural pneumonectomy for malignant pleural mesothelioma.   Ann Thorac Surg, 85(4): 1206-10.

BACKGROUND: Factors associated with increased risk of major complications after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma are not well characterized; in particular, the risks of induction chemotherapy and red blood cell (RBC) transfusion have not been well defined. METHODS: We reviewed our experience with 62 consecutive EPP (28 right sided) performed in our institution for malignant pleural mesothelioma between January 1993 and May 2007. A total of 44 patients ... [Abstract] [Full-text]

Articles on Mesothelioma published 19 March 2008:

Phase II trial of pemetrexed and gemcitabine in chemotherapy-naive malignant pleural mesothelioma.   J Clin Oncol, 26(9): 1465-71.

PURPOSE: Pemetrexed and gemcitabine have single-agent activity in malignant pleural mesothelioma (MPM). The combination of pemetrexed/gemcitabine has not previously been studied in MPM to our knowledge. PATIENTS AND METHODS: Patients with histologic or cytologic diagnosis of MPM were included. Cohort 1 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 8, and cohort 2 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 1. ... [Abstract] [Full-text]

Mesothelioma mortality in men: trends during 1977-2001 and projections for 2002-2016 in Spain.   Occup Environ Med, 65(4): 279-82.

OBJECTIVES: To evaluate mesothelioma death trends in Spain and to predict the number of future cases of mesothelioma. METHODS: After descriptive analysis of mesothelioma mortality data, an age-period-cohort model was applied to estimate future mesothelioma deaths. RESULTS: From 1977 to 2001, 1928 men over 35 years of age died of mesothelioma in Spain. Projections indicate that 1321 men are expected to die from mesothelioma between 2007 and 2016. CONCLUSION: It is expected that mesothelioma ... [Abstract] [Full-text]

Articles on Mesothelioma published 10 March 2008:

Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.   J Thorac Cardiovasc Surg, 135(3): 620-6, 626.e1-3.

OBJECTIVE: The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication. METHODS: Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were ... [Abstract] [Full-text]

A conditional mouse model for malignant mesothelioma.   Cancer Cell, 13(3): 261-71.

Malignant mesothelioma is a devastating disease that has been associated with loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. We introduced similar lesions in the mesothelial lining of the thoracic cavity of mice. Mesothelioma developed at high incidence in Nf2;Ink4a/Arf and Nf2;p53 conditional knockout mice with median survival times of approximately 30 and 20 weeks, respectively. Murine mesothelioma closely mimicked human malignant mesothelioma. ... [Abstract] [Full-text]

Articles on Mesothelioma published 28 February 2008:

Advances in the systemic therapy of malignant pleural mesothelioma.   Nat Clin Pract Oncol, 5(3): 136-47.

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines ... [Abstract] [Full-text]

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