Granulocyte/macrophage-colony-stimulating factor released by adenovirally transduced CT26 cells leads to the local expression of macrophage inflammatory protein …

T Kielian, E Nagai, A Ikubo, CA Rasmussen… - Cancer Immunology …, 1999 - Springer
T Kielian, E Nagai, A Ikubo, CA Rasmussen, T Suzuki
Cancer Immunology, Immunotherapy, 1999Springer
Antigen presenting cells (APC) play an essential role in the generation of tumor-specific
immune responses. Dendritic cells are the most potent of APC, capable of activating both
antigen-specific CD4+ and CD8+ T cells. Previously, we have described how vaccination of
mice with irradiated tumor cells producing granulocyte/macrophage-colony-stimulating
factor (GM-CSF) induces tumor-specific immunity capable of protecting mice from a
subsequent tumor challenge. The present study extends these findings to examine the types …
Abstract
Antigen presenting cells (APC) play an essential role in the generation of tumor-specific immune responses. Dendritic cells are the most potent of APC, capable of activating both antigen-specific CD4+ and CD8+ T cells. Previously, we have described how vaccination of mice with irradiated tumor cells producing granulocyte/macrophage-colony-stimulating factor (GM-CSF) induces tumor-specific immunity capable of protecting mice from a subsequent tumor challenge. The present study extends these findings to examine the types of APC infiltrating vaccination sites and the chemokines responsible for their recruitment. GM-CSF released from genetically engineered tumor cells led to the local accumulation of dendritic cells in and around the vaccination site. Quantification revealed a significant ten-fold increase in the number of dendritic cells infiltrating GM-CSF-producing as opposed to β-galactosidase-producing (control) vaccination sites. Reverse transcription/polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis of vaccination sites revealed that MIP-1α may be responsible for dendritic cell infiltration into GM-CSF-producing tissues. These findings suggest that GM-CSF may indirectly recruit dendritic cells into vaccination sites through the local production of MIP-1α.
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