Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

Interactions between Immune Cells and Tumor Cells / 대한갑상선학회지

Tumor microenvironment is defined as a heterogeneous complex composed of cancer cells, vascular endothelial cells, fibroblasts, and diverse immune cells. Cancer immunology is the study of interactions between the immune system and cancer cells which is applied to develop therapeutic strategies for human cancers. This review focused on tumor promoting myeloid derived cells such as tumor associated macrophages (TAM) and myeloid derived suppressor cells (MDSC) and their therapeutic applications.

Research progress on cancer therapy targeted at myeloid derived suppressor cells / 肿瘤研究与临床

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells of myeloid origin that comprises myeloid progenitor cells and immature macrophages, which expand in tumorbearing mice and patients' bone marrow, spleen and peripheral blood and recruit to the tumor site. MDSC express high levels of arginase 1 (ARG1), inducible-nitric oxide syntheses (iNOS), reactive oxygen species (ROS) and peroxynitrite. They could suppress T-cell functions by cell contact or not, and induce regulatory T cells (Treg), all of the above are its weapons to defend individuals' immune system. Anti-tumor strategies targeted at MDSC develop rapidly now. In this review, we briefly introduce the strategies that targeted at MDSC and their mechanisms.