title: T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Hematology, Department of Medicine at Huddinge, Division of Hematology, Department of Medicine at Solna, Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Norway. bjorn.wahlin@karolinska.se
authors.forename: Björn Engelbrekt
authors.initials: BE
authors.lastname: Wahlin
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Hans
authors.initials: H
authors.lastname: Hagberg
authors.forename: Martin
authors.initials: M
authors.lastname: Erlanson
authors.forename: Herman
authors.initials: H
authors.lastname: Nilsson-Ehle
authors.forename: Ola
authors.initials: O
authors.lastname: Lindén
authors.forename: Marie
authors.initials: M
authors.lastname: Nordström
authors.forename: Bjørn
authors.initials: B
authors.lastname: Ostenstad
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
authors.forename: Peter de Nully
authors.initials: Pde N
authors.lastname: Brown
authors.forename: Tuula
authors.initials: T
authors.lastname: Lehtinen
authors.forename: Martin
authors.initials: M
authors.lastname: Maisenhölder
authors.forename: Anne M
authors.initials: AM
authors.lastname: Tierens
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016131:Lymphocyte Subsets / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D000069283:Rituximab