Acute Myeloid Leukemia Cell-Intrinsic PD-1 Functions Promoting Leukemia Development By Recruiting SHP2

Acute myeloid leukemia (AML) is a devastating hematopoietic malignancy. With current therapies, only approximately 30% of patients achieve long-term survival. Therefore, novel, more active and less toxic treatments are urgently needed. Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways and inhibits T cell activation. Abnormally high PD-L1 expression on tumor cells and antigen-presenting cells in the tumor microenvironment mediates tumor immune escape, and PD-1/PD-L1 immune checkpoint blockade has showed promising results in cancer patients. Recently, PD-1 expressed on melanoma cells was also shown to play a pivotal role in tumor growth. To date, in AML, the function of PD-1 has been mainly studied in the host T cells, while little is known regarding the role of PD-1 in AML cells. Herein, we examined the level and role of PD-1 in AML cells using AML murine model and patient samples.