Elevated Chemokine Expression in the Bone Marrow of Patients with Myeloma and MGUS Is Associated with Marked Alterations in the Distribution of CD4+ and CD8+ T Cell Subsets within the Blood and Bone Marrow

Abstract 5076

Multiple Myeloma (MM) is a malignant disease of bone marrow plasma cells characterised by immune dysfunction and increased chemokine levels. We investigated chemokine receptor expression on T cells, particularly the Th1 and Th2-associated receptors, CXCR3 and CCR4, in patients with paraproteinaemia and compared this to controls and correlated this to the level of related chemokines in blood and bone marrow.

The frequency of CCR4+ T cells within the bone marrow was markedly increased in patients with MM and the normal distribution between blood and marrow was reversed. CXCR3+ Th1 Cells which were rare within normal marrow were increased relative to blood. Th17 CD4+ T cells were markedly increased within marrow with increased Th17 CD4+ CCR4+ and Th17 CD4+ CXCR3 populations and the suppressor CD25highCd127low FoxP3positive subset reduced within blood. The expression of the ligands for CCR4 and CXCR3 was markedly increased within the marrow of patients with MGUS and MM. Mesenchymal stem cells isolated from the bone marrow of myeloma patients supported T cell adhesion and migration with a preferential recruitment of CCR4 and CXCR3-positive cells. Chemokine gradients within the tumour microenvironment alter the distribution of major T cells subsets between blood and marrow. This pattern is established early in the development of paraproteinaemia and may offer a potential target for new forms of treatment.