Expression of Complement Regulatory Protein CD55 on Tumor Cells Has an Adverse Effect on the Outcome of Follicular Lymphoma Patients Treated with Immunochemotherapy

Abstract

The addition of rituximab to chemotherapy has considerably improved the outcome of follicular lymphoma (FL) patients, but the lengths of remissions are still variable. Activation of the C system has been shown to be an important effector mechanism of rituximab. The aim of this study was to evaluate whether differences in the expression of CD20 and C regulatory molecules (C-REG) in lymphoma cells correlate to the clinical course of FL. We used oligonucleotide microarray analysis to study mRNA levels of CD20, CD46 (MCP), CD55 (DAF) and CD59 (protectin) in the FL tissue of 23 patients treated with R-CHOP. The median follow-up time was 55 months. The patients were divided into long-term (progression free survival (PFS) >35 mo) and short-term (PFS <21 mo) responders, and mRNA levels were compared between the groups. High CD55 expression was observed more often in FL patients who relapsed early resulting in a shorter progression free survival (p=0.027). Median PFS time for patients with a low CD55 level was significantly longer than for those with high CD55 expression (not reached vs. 20 mo, p=0.003). The results were validated prospectively by analyzing the protein levels of CD20 and C-REGs with flow cytometry. The results of a pilot study of 12 FL patients showed that relative expression of CD20 to CD55 in CD20 positive cell population was higher in patients in remission in comparison to ones who relapsed. According to Kaplan-Meier estimates, the patients with low CD20/CD55 and CD20/C-REGave (average C regulator expression) ratios relapsed more often than the other patients. The results suggest that the expression of C regulators, especially of CD55, affects the efficacy of immunochemotherapy, and that C regulatory molecules represent an effective escape mechanism of immunochemotherapy in FL.