Decreased number of circulating DCs in late stage Follicular lymphoma patients
Follicular lymphoma (FL) is a malignant B cell cancer. The disease can be cured in early stages with radiotherapy; however, most patients are diagnosed in late stages. Within the last 10 years overall survival has improved due to combination therapies but the disease is still not curable. The dendritic cell (DC) is an important part of cellular immunity in and may be involved in the development of FL. The precise role of DCs in the development of FL is still unclear despite that DCs have been used in clinical vaccination trials in FL patients. Mature DCs are superior to immature DCs in stimulating a T-cell response against infection and cancer. Study aim and methods.
We analysed the DC population in peripheral blood from FL patients in different disease stages in order to unveil any disease stage associated differences. DCs were phenotyped using antibodies against the maturation markers HLA DR, HLA ABC, CD 80, CD 83, CD 86, the adhesion markers CCR5, CCR7, CD54,CD56, CD62L, and in addition the endocytosis marker CD205 and Fc gamma I receptor (CD32). Results.
We found that stage III/IV FL patients (n=8), who received chemotherapy, had a decreased total DC population(0,65%) compare to stage I FL patients (n=5), who received only radiotherapy(1,18%; p<0,01) and compared to healthy donors (n=9) (1,02%; p<0.02).HLA DR and HLA ABC expression was slightly higher in stage III/IV than stage I this difference was, however, not significant. We also found that CD 32 is only expressed on myeloid DC but not on plamacytoid DC, and that stage I FL patients have higher expression of CD32 than other FL groups and healthy donors. In addition, the leukocyte homing receptor CD62L is also highly expressed on stadium I FL DC compared to stadium III/IV and healthy donors. Conclusions.
The DC population in chemotherapy treated patients with stage III/IV FL is decreased. This finding is not due to a direct action of the chemotherapy as all patients in stadium III/IV had finished chemotherapy at least 6 months before testing. More plausible the reduction is associated with the late disease stage. Also, the DC expression of CD32 and CD62L is higher in early disease stage than in late stages of FL. Work is ongoing to evaluate functionality of the DCs.
Document Type: Abstract
Publication date: May 1, 2008