T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab

Bjorn Engelbrekt Wahlin, Christer Sundstrom, Harald Holte, Hans Hagberg, Martin Erlanson, Herman Nilsson-Ehle, Ola Lindén, Marie Nordstrom, Bjorn Ostenstad, Christian H. Geisler, Peter de Nully Brown, Tuula Lehtinen, Martin Maisenholder, Anne M. Tierens, Birgitta Sander, Birger Christensson, Eva Kimby

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38 Citations (SciVal)

Abstract

Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-alpha 2a-rituximab combinations. Results: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-alpha 2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-alpha 2a abrogates the negative impact of few CD8(+) cells. Clin Cancer Res; 17(12); 4136-44. (C) 2011 AACR.
Original languageEnglish
Pages (from-to)4136-4144
JournalClinical Cancer Research
Volume17
Issue number12
DOIs
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Cancer and Oncology

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