Leukemic progenitor cells enable immunosuppression and post-chemotherapy relapse via IL-36-inflammatory monocyte axis.

ABSTRACT: Chemotherapy can effectively reduce the leukemic burden and restore immune cell production in most acute myeloid leukemia (AML) cases. Nevertheless, endogenous immunosurveillance usually fails to recover after chemotherapy, permitting relapse. The underlying mechanisms of this therapeutic failure have remained poorly understood. Here, we show that abnormal IL-36 production activated by NF-κB is an essential feature of mouse and human leukemic progenitor cells (LPs). Mechanistically, IL-36 directly activates inflammatory monocytes (IMs) in bone marrow, which then precludes clearance of leukemia mediated by CD8⁺ T cells and facilitates LP growth. While sparing IMs, common chemotherapeutic agents stimulate IL-36 production from residual LPs via caspase-1 activation, thereby enablin

SUBMITTER: Guo HZ 

PROVIDER: S-EPMC8500518 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature