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

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-α2a-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-α2a 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-α2a abrogates the negative impact of few CD8(+) cells.

Sundström, ChristerUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)chrisund (author)
Holte, Harald (author)
Hagberg, HansUppsala universitet,Enheten för onkologi(Swepub:uu)hanshagb (author)
Erlanson, MartinUmeå universitet,Onkologi(Swepub:umu)maer0058 (author)
Nilsson-Ehle, Herman,1950Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xnilsh (author)
Lindén, OlaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-oli (author)
Nordström, Marie (author)
Ostenstad, Bjørn (author)
Geisler, Christian H (author)
Brown, Peter de Nully (author)
Lehtinen, Tuula (author)
Maisenhölder, Martin (author)
Tierens, Anne M (author)
Sander, BirgittaKarolinska Institutet (author)
Christensson, BirgerKarolinska Institutet (author)
Kimby, EvaKarolinska Institutet (author)
Karolinska InstitutetMolekylär och morfologisk patologi (creator_code:org_t)

In:Clinical Cancer Research: American Association for Cancer Research17:12, s. 4136-41441078-04321557-3265

By the author/editor: Wahlin, Björn En ...; Sundström, Chris ...; Holte, Harald; Hagberg, Hans; Erlanson, Martin; Nilsson-Ehle, He ...; show more...; Lindén, Ola; Nordström, Marie; Ostenstad, Bjørn; Geisler, Christi ...; Brown, Peter de ...; Lehtinen, Tuula; Maisenhölder, Ma ...; Tierens, Anne M; Sander, Birgitta; Christensson, Bi ...; Kimby, Eva; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Clinical Laborat ...

By the university: Umeå University; Uppsala University; Karolinska Institutet; University of Gothenburg; Lund University

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