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Clinical Cancer Research Vol. 11, 1467-1473, February 2005
© 2005 American Association for Cancer Research

Imaging, Diagnosis, Prognosis

Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells

Tomás Álvaro1, Marylène Lejeune1, Ma Teresa Salvadó1, Ramón Bosch1, Juan F. García2, Joaquín Jaén1, Alison H. Banham5, Giovanna Roncador3, Carlos Montalbán4 and Miguel A. Piris2

1 Department of Pathology, Hospital Verge de la Cinta, Tortosa, Spain; 2 Molecular Pathology Programme and 3 Monoclonal Antibodies Unit, Centro Nacional de Investigaciones Oncologicas; 4 Department of Internal Medicine, Hospital Ramon y Cajal, Madrid, Spain; and 5 Nuffield Department of Clinical Laboratory Sciences, Leukaemia Research Fund Immunodiagnostics Unit, John Radcliffe Hospital, Oxford, United Kingdom

Requests for reprints: Tomás Álvaro-Naranjo, Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/ Esplanetes n° 14, 43500-Tortosa, Spain. Phone: 34-977-519104; Fax: 34-977-519104; E-mail: talvaro.htvc.ics{at}gencat.net.

Purpose: Recent studies of Hodgkin's lymphoma (HL) have suggested that the presence of regulatory T cells in the reactive background may explain the inhibition of the antitumoral host immune response observed in these patients. This study aimed to assess the relevance of regulatory T cells and CTLs present in the background of HL samples in the prognosis of a series of classic HL (cHL) patients.

Experimental Design: Expression of granzyme B and TIA-1 (markers for CTL) and FOXP3 (a marker for regulatory T cells) were evaluated independently by immunohistochemistry in tissue microarrays of 257 cHL patients and correlated with patient outcome.

Results: The combined influence of the presence of FOXP3+ and TIA-1+ cells distinguished three risk groups of patients with 5-year overall survival of 100%, 88%, and 73%. The presence of a small number of FOXP3+ cells and a high proportion of TIA-1+ cells in the infiltrate represent an independent prognostic factor that negatively influenced event-free survival and disease-free survival in cHL. Compared with the features at diagnosis, relapsed samples tended to have more TIA-1+ cells and a lower proportion of FOXP3+ cells in the reactive background.

Conclusions: These data suggest that low infiltration of FOXP3+ cells in conjunction with high infiltration of TIA-1+ cells in cHL may represent biological markers predicting an unfavorable outcome. Moreover, the variation of these markers over the course of the disease implies a possible role for them in the progression of HL cases.

Key Words: Immunohistochemistry • CTL • FOXP3 • immune response • survival




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