Hematopoietic and immune microenvironment (HIM)

The hematopoietic and immune microenvironment (HIM) is a specialized anatomical niche, primarily located within the bone marrow, that governs the production, maintenance, and differentiation of blood and immune cells (Pinho & Frenette, 2019). It consists of a complex interplay between various cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and sympathetic neurons, as well as extracellular matrix components and soluble factors like CXCL12 and stem cell factor (SCF) (Nakamura-Ishizu et al., 2020). This microenvironment is essential for maintaining hematopoietic stem cell (HSC) quiescence and responding to systemic demands such as infection or blood loss. In diseases like leukemia and multiple myeloma, the HIM is often co-opted or hijacked to create a protective sanctuary that shields malignant cells from chemotherapy and immune-mediated destruction (Tikhonova et al., 2020). Therapeutic strategies targeting this environment, such as the use of CXCR4 antagonists like plerixafor, aim to disrupt these protective interactions and mobilize cells into the peripheral blood for easier eradication. However, targeting this system presents challenges, as disrupting the niche can lead to unintended consequences like healthy stem cell exhaustion or impaired immune reconstitution.

Other names

Bone marrow microenvironmentHematopoietic stem cell nicheHSC nicheImmune microenvironmentBone marrow nicheHematopoietic niche

Drugs targeting this environment typically work by disrupting the adhesive interactions between hematopoietic cells and their supporting stroma, mobilizing stem or malignant cells into the peripheral circulation, or modulating the cytokine and chemokine milieu to restore normal hematopoiesis or enhance anti-tumor immunity (Nakamura-Ishizu et al., 2020; Tikhonova et al., 2020).