Reactive myelopoiesis and the onset of myeloid-mediated immune suppression: Implications for adoptive cell therapy

Abstract

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of cancer, providing long-term regressions in patients. However, only a minority of patients that receive ACT with tumor-specific T cells exhibit durable benefit. Thus, there is an urgent need to characterize mechanisms of resistance and define strategies to alleviate immunosuppression in the context of ACT in cancer. This article reviews the importance of lymphodepleting regimens in promoting the optimal engraftment and expansion of T cells in hosts after adoptive transfer. In addition, we discuss the role of concomitant immunosuppression and the accumulation of myeloid derived suppressor cells (MDSCs) during immune recovery after lymphodepleting regimens and mobilization regimens.

Keywords: Adoptive T cell therapy; Cyclophosphamide; Fludarabine; G-CSF; Hematopoiesis; Immunosuppression; Lymphodepletion; MDSCs; Myelopoiesis.