Abstract
Trilaciclib, a transient cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, was developed to protect hematopoietic stem and progenitor cells (HSPCs) from cytotoxic injury by inducing a reversible G1 arrest at the time of chemotherapy exposure. Beyond its role in reducing chemotherapy-induced myelosuppression in small-cell lung cancer, interest has broadened to its effects on the myeloid compartment—spanning granulopoiesis, monocyte/macrophage biology, dendritic cell function, and the interplay between emergency hematopoiesis and antitumor immunity. This perspective synthesizes mechanistic underpinnings, preclinical and clinical observations relevant to myeloid hematopoiesis, and translational opportunities. We argue that trilaciclib’s “myelo-protective” and “immune-tuning” properties can be systematically harnessed in rational combinations and biomarker-driven regimens.