CD8+T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma

Purpose: 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. Experimental Design: 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 CIS 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.