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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

The dysfunction and abnormal signaling pathway of dendritic cells loaded by tumor antigen can be overcome by

Deok-Hwan Yang1, Jung-Sun Park, Chun-Ji Jin

  • 1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeonnam, South Korea.

Leukemia Research
|October 17, 2008
PubMed

We investigated whether dendritic cells (DCs) from multiple myeloma (MM) patients were affected by loading tumor antigens and whether the defective DC function associated with MM could be overcome by the neutralization of VEGF. MM-specific DCs were generated by loading tumor lysates from myeloma cells at diagnosis or relapsed/progressive state, respectively. DCs loaded with tumor lysates showed lower phenotypic maturation, less T cell stimulatory capacity, less cytotoxic T lymphocyte activities, and highly abnormal cytokine secretions of IL-6 and IL-12, compared to myeloma lysate-unloaded DCs. The levels of VEGF, phospho-STAT3 and phospho-ERK1/2 in DCs were significantly higher with loading myeloma lysates. After the neutralization of VEGF activity, the DC function, signal transduction and cytokine production returned to normal. The defective function of DC in patients with MM is significantly affected by loading tumor antigens, correlating with abnormal STAT3 and the NF-kappaB signaling pathway, and neutralization of VEGF can overcome this DC dysfunction through the elimination of abnormal signal transduction.

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