Inhibiting p38 MAPK signaling restores dendritic cell function in multiple myeloma

06-02-2006

Inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma.

According to recent research from the United States, "Dendritic cells (DCs) from patients with cancer are functionally defective, but the molecular mechanisms underlying these defects are poorly understood. In this study, we used the murine 5TGM1 myeloma model to examine the effects and mechanisms of tumor-derived factors on the differentiation and function of DCs."

"Myeloma cells or tumor culture conditioning medium (TCCM) were shown to inhibit the differentiation and function of BM-derived DCs (BMDCs), as evidenced by the down-regulated expression of DC-related surface molecules, decreased IL-12, and compromised capacity of the cells to activate allospecific T cells," said Siqing Wang and colleagues at the M.D. Anderson Cancer Center. "Moreover, TCCM-treated BMDCs were inferior to normal BMDCs at priming tumor-specific immune responses in vivo. Neutralizing antibodies against IL-6, IL-10, and TGF-beta partially abrogated the effects."

"TCCM treatment activated p38 mitogen-activated protein kinase (MAPK) and Janus kinase (JNK) but inhibited extracellular regulated kinase (ERK). Inhibiting p38 MAPK restored the phenotype, cytokine secretion, and function of TCCM-treated BMDCs," reported the scientists. "BMDCs from cultures with TCCM and p38 inhibitor was as efficacious as normal BMDCs at inducing tumor-specific antibody, type 1 T cell, and cytotoxic T lymphocyte (CTL) responses and at prolonging mouse survival."

The scientists concluded, "Thus, our results suggested that tumor-induced p38 MAPK activation and ERK inhibition in DCs may be a new mechanism for tumor evasion and that regulating these pathways during DC differentiation provides new strategies for generating potent DC vaccines for immunotherapy in patients with cancer."

Wang and associates published their study in Blood (Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma. Blood, 2006;107(6):2432-2439).

For additional information, contact Qing Yi, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Unit 0903, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail:

Publisher contact information for the journal Blood is: American Society of Hematology, 1900 M Street NW, Suite 200, Washington, DC 20036, USA.

Keywords: Houston, Texas, United States, Multiple Myeloma Vaccine, Cancer Vaccine, Dendritic Cell Vaccine, Vaccine Development, Immunology, Immunotherapy, Oncology, Proteomics.

This article was prepared by Cancer Vaccine Week editors from staff and other reports. Copyright 2006, Cancer Vaccine Week via NewsRx.com.