Immune regulatory cells within the bone marrow and systemic immune milieu

The immune regulatory cells within the bone marrow and systemic immune milieu represent a complex network of immunosuppressive and homeostatic cell populations, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and regulatory B cells (Bregs). In the bone marrow, these cells reside in specialized niches where they maintain hematopoietic stem cell (HSC) homeostasis and create an immune-privileged environment that protects the marrow from excessive inflammation (Fujisaki et al., 2011). However, in diseases such as multiple myeloma, this suppressive milieu is co-opted by malignant cells to evade the host immune system and promote tumor survival (Ghobrial et al., 2015). Systemically, these regulatory populations circulate to maintain peripheral tolerance and prevent autoimmunity. Therapeutic targeting of this milieu often involves the use of monoclonal antibodies, such as daratumumab, which depletes CD38-positive regulatory cells to restore anti-tumor T-cell activity (Krejcik et al., 2016). Other approaches include the use of immunomodulatory drugs (IMiDs) like lenalidomide and proteasome inhibitors like bortezomib that alter the cytokine profile and cellular composition of the bone marrow niche. Understanding the interplay between these cells and the systemic immune environment is essential for developing effective immunotherapies and managing conditions like graft-versus-host disease (Le Texier et al., 2021). This target is more accurately characterized as a cellular compartment or microenvironment rather than a single molecular entity.

Other names

Bone marrow immune microenvironmentBone marrow immune nicheCD38+ immune regulatory cellsBM-TregsMyeloid-derived suppressor cells (MDSCs)Regulatory T cells (Tregs)

Therapeutic agents targeting this milieu act by depleting immunosuppressive cell populations (e.g., CD38+ Tregs and MDSCs), modulating cytokine signaling (e.g., IL-6, TNF-alpha), or disrupting the physical and chemical interactions within the bone marrow niche to restore anti-tumor immunity or promote hematopoietic recovery.