Interleukin-1-mediated inflammatory memory: Protective training or maladaptive tumor imprinting?

Interleukin-1 (IL-1) exerts a pivotal role in the regulation of innate immune responses and inflammatory processes. Beyond its local effects at the site of inflammation, IL-1 acts as a systemic regulator of hematopoiesis by reprogramming hematopoietic stem and progenitor cells (HSPCs), thereby shaping the functional properties of the myeloid progeny. Through induction of emergency myelopoiesis and inflammatory memory, IL-1 can imprint durable epigenetic, metabolic and transcriptomic changes within the hematopoietic compartment, altering immune output well beyond the initial inflammatory trigger. This systemic effect of IL-1 signaling is particularly relevant in the context of cancer, since tumors are now viewed as inflammatory entities providing persistent inflammatory factors that can influence hematopoiesis and imprint an immunosuppressive phenotype in myeloid cells. In parallel, aging and clonal hematopoiesis (CH) are characterized by chronic low-grade inflammation in which IL-1 signaling may amplify mutant progenitor expansion, linking inflammaging to increased susceptibility to both hematological malignancies and solid cancers. Here, we discuss the role of IL-1 signaling in emergency myelopoiesis and both central and peripheral inflammatory memory, and how these processes shape cancer progression. We also highlight the therapeutic potential of targeting IL-1-mediated hematopoietic reprogramming.