title: CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma.
abstract: OBJECTIVE
  Follicular lymphoma is a heterogeneous disease with variable prognosis and clinical course. We hypothesized that the presence of nonmalignant T cells in the microenvironment of the tumor may affect the outcome.
  
  
  METHODS
  Using flow cytometry, we evaluated the T-cell subsets in the lymph node microenvironment of follicular lymphoma. All patients in South Stockholm County with indolent follicular lymphoma and with flow cytometry done on a diagnostic lymph node between 1994 and 2004 were included (N = 139). Diagnosis and grade (1, 2, and 3a) were confirmed by re-review. Flow cytometry results were reanalyzed. Lymphocyte subsets, the Follicular Lymphoma International Prognostic Index, grade, and clinical characteristics were evaluated in univariable and multivariable Cox analysis with respect to overall survival (OS) and disease-specific survival (DSS).
  
  
  RESULTS
  Higher CD8+ T-cell levels correlated with longer OS and DSS, independently of the Follicular Lymphoma International Prognostic Index (OS, P = 0.017; DSS, P = 0.020) and independently of all other prognostic factors (OS, P = 0.001; DSS, P = 0.004). Median OS was not reached for patients in the upper quarter of CD8+ T-cell levels (>8.6%), 10.4 years for patients in the middle half (4.2-8.6%), and 6.0 years for patients in the lower quarter (<4.2%). Furthermore, patients who had not required treatment within 6 months from diagnosis had more CD8+ T cells (P = 0.011).
  
  
  CONCLUSIONS
  Higher levels of CD8+ T cells predict a better prognosis, and these data support an important role for nonmalignant immune cells in the biology of follicular lymphoma. Evaluating the CD8+ T cells by flow cytometry at diagnosis may provide prognostic information.
authors.affiliation: Division of Hematology, Department of Internal Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden. bjorn.wahlin@karolinska.se
authors.forename: Björn Engelbrekt
authors.initials: BE
authors.lastname: Wahlin
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008224:Lymphoma, Follicular / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome