Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia

Venugopal, Parameswaran; Sivaraman, S.; Huang, Xiaoke; Nayini, Jaya; Gregory, Stephanie A.; Preisler, Harvey D.

doi:10.1016/s0145-2126(99)00206-4

Cited by 73 publications

(44 citation statements)

References 15 publications

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“…There are only a few reports demonstrat- ing a cytokine (IL-4, GM-CSF, or IFN-␣)-mediated increase in CD20 surface expression (28,29). Transcriptional up-regulation of CD20 dependent on ERK phosphorylation was reported by Wojciechowski et al (30) in lymphoma and primary CLL cells treated with bryostatin-1.…”

Section: Discussionmentioning

confidence: 95%

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Winiarska

Nowis

Bil

et al. 2012

Journal of Biological Chemistry

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Background:The influence of farnesyltransferase inhibitors (FTIs) on CD20 levels is unknown. Results: FTIs increase CD20 expression and improve rituximab-mediated activation of complement-dependent cytotoxicity. Conclusion: FTIs sensitize tumor cells to anti-CD20 mAbs. Significance: The combination of FTIs with anti-CD20 mAbs seems to be a reasonable therapeutic approach worth to be tested in patients with B-cell tumors.

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Section: Discussionmentioning

confidence: 95%

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Winiarska

Nowis

Bil

et al. 2012

Journal of Biological Chemistry

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“…These immunostimulatory sequences induce secretion of numerous cytokines (IL-12, IL-18, IFN-a, and IFN-h) by macrophages and dendritic cells (25, 48 -50). On the other hand, strategies that enhance complement fixation of anti-CD20 antibodies or that induce an up-regulation of CD20 expression, such as cytokine treatment, or the use of immune modulator agents, such as bryostatin-1, may improve CD20-targeted cell kill of low CD20-expressing cells (30,51,52). In addition, blocking of the CRPs CD55 or CD59 may increase the sensitivity to complement (7,11).…”

Section: Discussionmentioning

confidence: 99%

Complement-Induced Cell Death by Rituximab Depends on CD20 Expression Level and Acts Complementary to Antibody-Dependent Cellular Cytotoxicity

Meerten

Rijn

Hol

et al. 2006

Clinical Cancer Research

221

151

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Purpose:The use of the CD20-specific antibody rituximab has greatly improved the response to treatment of CD20 + follicular lymphoma. Despite the success of rituximab, resistance has been reported and prognostic markers to predict individual response are lacking. The level of CD20 expression on tumors has been related to response, but results of several studies are contradictory and no clear relationship could be established. Complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) are thought to be important effector mechanisms, but the exact mechanism of rituximab-mediated cell kill is still unknown. Importantly, no data have been reported on the combined contribution of CDC and ADCC. Experimental Design: We have developed a system of clonally related CEM-CD20 cells by retroviral transfer of the human CD20 cDNA (n = 90). This set of cells, with the CD20 molecule as the only variable, was used to study the importance of CD20 expression level on rituximabmediated CDC, ADCC, and the combination. Results: We show a sigmoidal correlation of CD20 expression level and rituximab-mediated killing via CDC but not ADCC. On both high and low CD20-expressing cells, all CD20 molecules were translocated into lipid rafts after rituximab binding. Furthermore, CDC and ADCC act simultaneously and CDC-resistant cells are sensitive to ADCC and vice versa. Conclusions:These findings suggest that CDC depends on CD20 expression level and that both CDC and ADCC act complementary.These data give new insights into novel strategies to improve the efficacy of CD20-specific antibodies for the treatment of CD20 + tumors.

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“…Recent studies have reported that IL-4, GM-CSF, TNF-␣, and IFN-␣ are able to induce CD20 surface expression on B cells from CLL patients (55)(56)(57)(58). However, the mechanisms regulating the expression of CD20 remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms

Wojciechowski

Marshall

et al. 2005

The Journal of Immunology

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Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted cells. Although the majority of B cell malignancies express the CD20 Ag, only ∼50% of patients will respond to single-agent rituximab. The available data suggest that a decreased CD20 expression could account for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. We evaluated the effect of the immune modulator agent bryostatin-1 on the expression of CD20 in non-Hodgkin’s lymphoma cells. Using the B cell lines, DB and RAMOS, as well as tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The enhanced expression of CD20 was associated with increased transcriptional activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected. The effect of bryostatin-1 on CD20 expression in non-Hodgkin’s lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the first time that ERK phosphorylation is required for the up-regulated expression of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and rituximab could be a valuable combined therapy for B cell malignancies.

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Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia

Cited by 73 publications

References 15 publications

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Complement-Induced Cell Death by Rituximab Depends on CD20 Expression Level and Acts Complementary to Antibody-Dependent Cellular Cytotoxicity

Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms

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