Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes

Immune dysregulation is a defining feature of myelodysplastic syndromes (MDS). Recently, several studies have further defined the complex role of immune alterations within MDS. Herein, we will summarize some of these findings and discuss the therapeutic strategies currently in development. Immune alterations in MDS are complex, heterogeneous, and intertwined with clonal hematopoiesis and stromal cell dysfunction. Inflammation in MDS proceeds as a vicious cycle, mediated in large part by secreted factors, which induce cell death and activate innate immune signaling. Therapeutic targeting of this variable immune dysregulation has led to modest responses thus far, but incorporation of the growing repertoire of immunotherapy brings new potential for improved outcomes. The immune milieu is variable across the spectrum of MDS subtypes, with a changing balance of inflammatory and suppressive cellular forces from low- to high-risk disease.