Monocytic Cell Variations in Postallotransplant Environment: Balancing Graft Versus Host Disease and Graft‐Versus‐Leukemia Effect

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for various hematologic malignancies. However, its success is critically dependent on maintaining the delicate balance between the beneficial graft‐versus‐leukemia (GvL) effect and the harmful graft‐versus‐host disease (GvHD). This review highlights the increasingly recognized role of monocyte‐derived cell populations in modulating posttransplant immune responses. We explore the functions of distinct monocytic subpopulations—classical, intermediate, and nonclassical monocytes—and their involvement in both immune reconstitution and the pathogenesis of GvHD. Intermediate and nonclassical monocytes have been associated with proinflammatory responses, particularly through induction of Th17 and Th1 cells, thus contributing to acute and chronic GvHD (cGvHD) development. In contrast, early recovery of classical monocytes correlates with improved overall survival and reduced relapse risk. Additionally, the review discusses the dual role of macrophages, with M1 macrophages enhancing inflammatory responses and GvL activity, while M2 macrophages promote tissue repair and fibrosis, particularly in cGvHD. Leukemia‐associated macrophages (LAMs) are implicated in immune escape and disease relapse due to their immunosuppressive phenotype and checkpoint expression. Finally, we examine the suppressive functions of myeloid‐derived suppressor cells (MDSCs), especially monocytic MDSCs (M‐MDSCs) and polymorphonuclear MDSCs (PMN‐MDSCs) subsets. These cells modulate T‐cell responses and may help mitigate GvHD without compromising GvL, although their exact role remains debated. Understanding the nuanced roles of these monocytic populations may open new avenues for improving alloHSCT outcomes by selectively enhancing GvL while preventing or attenuating GvHD.