The Effect of Gefitinib on Immune Response of Human Peripheral Blood Monocyte-Derived Dendritic Cells.

Cho, Jin Hoon; Kim, Mi Hyun; Lee, Kwang Ha; Kim, Ki Uk; Jeon, Doo Soo; Park, Hye Kyung; Kim, Yun Seong; Lee, Min Ki; Park, Soon Kew

doi:2010.69.6.456

Tuberc Respir Dis > Volume 69(6); 2010 > Article

Original Article

Tuberculosis and Respiratory Diseases 2010;69(6):456-464.
DOI: https://doi.org/10.4046/trd.2010.69.6.456 Published online December 1, 2010.

The Effect of Gefitinib on Immune Response of Human Peripheral Blood Monocyte-Derived Dendritic Cells.

Jin Hoon Cho, Mi Hyun Kim, Kwang Ha Lee, Ki Uk Kim, Doo Soo Jeon, Hye Kyung Park, Yun Seong Kim, Min Ki Lee, Soon Kew Park

Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea. leemk@pusan.ac.kr

Abstract

BACKGROUND
Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). METHODS: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-alpha (10 ng/mL), IL-1beta (10 ng/mL), IL-6 (1,000 U/mL) and PGE2 (1 micro/mL). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with [3H]-thymidine uptake assay was done. RESULTS: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under 10 microM of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. CONCLUSION: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under 10 microM of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.

Key Words: Dendritic cells, gefitinib, Interleukin-12, Apoptosis