Characterization of tumor response after administration of rituximab in
pediatric B-NHL
Abstract
Background Mature aggressive B-cell lymphoma are heterogenous
malignancies that make up more than half of all diagnosed Non-Hodgkin
lymphoma in children and adolescents. The overall survival rate
increased over the last decades to 80–90%, due to fine tuning of
polychemotherapy. However, new therapeutic implications are needed to
further increase the overall survival. Current clinical trials analyze
the therapeutic effect of rituximab in pediatric patients, while the
mechanism of action in vivo is still not fully understood. Methods
Effector molecules important for tumor defense were analyzed before and
at day five after rituximab treatment via flow cytometry. Serum
rituximab levels were measured with an ELISA. Results We evaluated
patient parameters that may affect treatment response in relation to
rituximab administration and serum rituximab levels. We indeed found a
reduction of FcγRII levels after rituximab treatment in monocyte
subtypes, while FcγRI expression was significantly increased, pointing
to exhaustion of FcγRII mediated B cell depletion and compensation via
FcγRI mediated trogocytosis. Serum levels of proinflammatory marker
proteins S100A8/A9 and S100A12 significantly decreased after treatment
to normal levels from an overall proinflammatory state before treatment.
CD57, perforin and granzyme B expression decreased after treatment,
probably due to exhaustion of NK cells. Conclusion The highlighted
effects of rituximab treatment on patient’s immune response help
understanding the biology behind tumor defense mechanisms and effector
function. After subsequent studies, these novel insights might be
translated into patient care and could contribute to improve treatment
of pediatric patients with mature aggressive B-cell lymphoma.