HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Masaki Anraku Li Zhang Shaf Keshavjee Michael R. Johnston Marc de Perrot Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Anraku, M. Articles by de Perrot, M. Search for Related Content PubMed Articles by Anraku, M. Articles by de Perrot, M. Related Collections Lung - cancer Pleura

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

^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.