Chemotherapy Target Responsible for Graft-Versus-Host-Disease

A protein linked to the development of graft-versus-host disease (GVHD) following bone marrow transplantation has been identified as a target for chemotherapy, since its removal prevents this syndrome without impinging on the immune system's ability to attack residual leukemia cells (graft-versus leukemia [GVL] response).

Investigators at the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL, USA) worked with a mouse model. They showed that T cell responses triggered in mice by either Listeria monocytogenes or administration of antigen and adjuvant were relatively well preserved in the absence of the theta isoform of protein kinase C (PKC-theta). In contrast, PKC-theta was required for the generation of an immune response to some foreign proteins and GVHD induction. Absence of PKC-theta raised the threshold for T cell activation, which selectively affected the level of the immune response. Most importantly, PKC-theta-deficient T cells retained the ability to respond to virus infection and to induce the GVL effect after bone marrow transplantation.

Removing PKC-theta prevented GVHD but allowed the immune system to mount a GVL response against residual leukemia cells and against infectious agents. To summarize, the investigators wrote in the November 9, 2009, issue of the Journal of Clinical Investigation that, "These findings suggest PKC-theta is a potentially unique therapeutic target required for GVHD induction but not for GVL or protective responses to infectious agents."

Related Links:
H. Lee Moffitt Cancer Center and Research Institute