TY - JOUR
T1 - T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
AU - Wahlin, Bjorn Engelbrekt
AU - Sundstrom, Christer
AU - Holte, Harald
AU - Hagberg, Hans
AU - Erlanson, Martin
AU - Nilsson-Ehle, Herman
AU - Lindén, Ola
AU - Nordstrom, Marie
AU - Ostenstad, Bjorn
AU - Geisler, Christian H.
AU - Brown, Peter de Nully
AU - Lehtinen, Tuula
AU - Maisenholder, Martin
AU - Tierens, Anne M.
AU - Sander, Birgitta
AU - Christensson, Birger
AU - Kimby, Eva
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1158/1078-0432.CCR-11-0264
DO - 10.1158/1078-0432.CCR-11-0264
M3 - Article
SN - 1078-0432
VL - 17
SP - 4136
EP - 4144
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -
