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Masaki Anraku
Li Zhang
Shaf Keshavjee
Michael R. Johnston
Marc de Perrot
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J Thorac Cardiovasc Surg 2008;135:823-829
© 2008 The American Association for Thoracic Surgery

General Thoracic Surgery

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

Masaki Anraku, MDa, Kristopher S. Cunningham, MD, PhDb, Zhihong Yun, BSa, Ming-Sound Tsao, MDb, Li Zhang, PhDc, Shaf Keshavjee, MDa, Michael R. Johnston, MDa, Marc de Perrot, MDa,*

a Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada
b Division of Applied Molecular Oncology, Ontario Cancer Institute, University Health Network, University of Toronto, Ontario, Canada
c Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, University of Toronto, Ontario, Canada

Received for publication April 22, 2006; revisions received July 2, 2007; accepted for publication October 26, 2007.

* Address for reprints: Marc de Perrot, MD, MSc, Toronto General Hospital 9N-961, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. (Email: marc.deperrot{at}uhn.on.ca).

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.

Abbreviations and Acronyms EPP = extrapleural pneumonectomy; MPM = malignant pleural mesothelioma; TIL = tumor-infiltrating lymphocyte; TUNEL = deoxyuride-5'-triphosphate biotin nick end labeling




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