The chemokine system in allogeneic stem-cell transplantation: a possible therapeutic target?

Abstract

Further improvements in allogeneic stem-cell transplantation will probably depend on a better balance between immunosuppression to control graft-versus-host disease and immunological reconstitution sufficient to ensure engraftment, reduction of infection-related mortality and maintenance of post-transplant antileukemic immune reactivity. The chemokine network is an important part of the immune system, and, in addition, CXCL12/CXCR4 seem to be essential for granulocyte colony-stimulating factor-induced stem-cell mobilization. Partial ex vivo graft T-cell depletion based on the expression of specific chemokine receptors involved in T-cell recruitment to graft-versus-host disease target organs may also become a future therapeutic strategy; an alternative approach could be pharmacological inhibition (single-receptor inhibitors or dual-receptor inhibitors) in vivo of specific chemokine receptors involved in this T-cell recruitment. Future clinical studies should therefore be based on a better characterization of various immunocompetent cells, including their chemokine receptor profile, both in the allografts and during post-transplant reconstitution.

Chemotaxis-driven disease-site targeting of therapeutic adult stem cells in dystrophic epidermolysis bullosa

“…Being secreted from cells in damaged peripheral tissue, chemokines recruit chemokine receptor-expressing cells, such as leukocytes, and possibly stem cells as part of host defense and repair mechanisms. The crucial role of chemokines in directional migration of ASC to various tissues, such as the heart, lung, bone marrow, and intestine, has been demonstrated previously [14, 15]. Thus, knowledge of chemokines expressed by the targeted tissue and cognate chemokine receptors expressed on the surface of the targeted stem cells is a prerequisite for successful targeting of therapeutic ASC.…”

The Chemokine Superfamily Revisited

“…High CXCL10 concentrations may also correlate with poor prognosis and metastasis in colorectal cancer (Toiyama et al, 2012). More information on this subject can be found here (Amanatidou et al, 2011; Balkwill, 2012; Melve et al, 2011). …”

The Possible Diagnostic and Prognostic Use of Systemic Chemokine Profiles in Clinical Medicine—The Experience in Acute Myeloid Leukemia from Disease Development and Diagnosis via Conventional Chemotherapy to Allogeneic Stem Cell Transplantation

“…These mediators may not only be important as diagnostic and prognostic markers of acute GVHD, they may also represent possible therapeutic targets in the treatment of this posttransplant complication. Firstly, chemokine receptors are now being developed, including inhibitors of the two receptors, CXCR1 and CXCR2, that show approximately 78% sequence identity and bind CXCL8 [116,117]. CXCL8 is important, both for development of angiogenesis and for T-cell chemotaxis [42,117]; CXCR1/CXCR2 inhibition may thus have several beneficial effects in these patients, including (i) inhibition of GVHD associated angiogenesis; (ii) inhibition of T-cell recruitment to GVHD-affected organs and (iii) possibly an antileukemic effect with reduction of posttransplant relapse risk through inhibition of local angiogenesis induced by residual leukemia cells.…”