Immunoregulation of Human Myeloid Dendritic Cells and Monocytes by Vascular Endothelial Growth Factor,

Abstract 3212

Vascular endothelial growth factor (VEGF), produced by many tumours including multiple myeloma (MM), has been reported to regulate the function of myeloid cells inducing myeloid-derived suppressor cells that suppress T cell responses. Little is known about the effect of VEGF on human myeloid cells including myeloid dendritic cells (MDC) and monocytes during their lifespan in bone marrow (BM) and peripheral blood (PB). We analysed the capacity of rhVEGF₁₆₅ to regulate_. MDC (CD11c⁺CD16⁺MDC and CD11c⁺CD16⁻MDC) and CD14⁺ monocytes that reside in the BM of humanised (hu)NOD/SCID mice or in peripheral blood (PB) of adult healthy subjects.

The CD11c⁺CD16⁻MDC and monocytes located in the femur, tibia and pelvic bones had elevated VEGFR-1 and VEGFR-2 surface expression compared to those located in the vertebrae and skull. Surface expression of VEGFR-1 and VEGFR-2 was negligible on CD11c⁺CD16⁺MDC, CD11c⁺CD16⁻MDC and monocytes in PB, however, VEGFR-1 mRNA was detected in CD11c⁺CD16⁺MDC and monocytes, and VEGFR-1 and VEGFR-2 mRNA in CD11c⁺CD16⁻DC. Treatment with rhVEGF₁₆₅ had no effect on maturation status of MDC and monocytes residing in BM and PB, as measured by MHC-class II, CD40, CD86, CD83 expression. However, rhVEGF₁₆₅ treatment regulated the capacity of MDC and monocytes to stimulate T cell responses by inducing several disparate outcomes, enhancing the capacity of CD11c⁺CD16⁻MDC, diminishing the capacity of monocytes and no effect on CD11c⁺CD16⁺MDC.

Our data suggests that the paradigm of VEGF-induced myeloid-derived suppressor cells is not as simple as originally predicted and it is likely that VEGF regulates myeloid cells to varying degrees depending on their developmental status.