Concise Review: Modulating Cancer Immunity with Hematopoietic Stem and Progenitor Cells

Abstract

Hematopoietic stem and progenitor cells (HSPCs) are the progenitor cells that can regenerate the entire blood compartment, including the immune system. Recent studies have unearthed considerable immune‐modulating potential of these cells. They can migrate through chemotactic gradients, differentiate into functional immune cells, and crosstalk with immune cells during infections, autoimmune diseases, and cancers. Although the primary role of HSPCs during solid malignancies is considered immunosuppressive, recent studies have discovered immune‐activating HSPCs and progeny. In this review, we will discuss the recent evidence that HSPCs act as immunomodulators during solid cancers and highlight the future directions of discovery. S tem C ells 2019;37:166–175

Tumor-educated monocyte-dendritic progenitors promote a metastatic switch

“…Next, since tumor progression is associated with pronounced myelopoiesis (Wu et al, 2014), with the focus on the BM niche, we quantified myeloid and lymphoid cells in the BM compartment of naïve and tumor-bearing mice. Tumor-bearing mice exhibited an increase in myeloid cells and a decrease in lymphoid-derived B and T cells, in comparison to the tumor-free control group, in a comparable way to their changes in the tumor mass, as previously reported (Wildes et al, 2019). Importantly, the increased ratio of myeloid to lymphoid derived cells in the BM compartment was most pronounced in mice implanted with met-high tumors (Fig.…”

“…In fact, sustained met-high educated HSPC specific differentiation suggests the involvement of epigenetic modifications that might regulate their programming, a process that should be further elucidated. Furthermore, while there is an overwhelming amount of evidence for HSPCs giving rise to MDSCs in tumor conditions (Wildes et al, 2019), we found that LSK cells educated by met-low or met-high tumor conditions exhibit an MDSC phenotype, with specific differentiation program which further gives rise to M2 macrophages only in met-high tumors. Indeed, studies have demonstrated that myeloid cells and tumor-associated immunosuppressive macrophages (M2 macrophages) home to the pre-metastatic sites where they contribute to the recruitment and retention of circulating tumor cells (Condamine et al, 2015; Doak et al, 2018; Giles et al, 2016).…”

“…Accumulating evidence suggests that tumors affect hematopoiesis (Wildes et al, 2019). The BM compartment is highly responsive to various conditions, including infection, inflammation and cancer (Hoggatt et al, 2016;Wilson et al, 2008).…”

“…A recent study demonstrated that the composition of circulating HSPCs is significantly altered in patients with solid tumors, with increased levels of granulocyte-monocyte progenitors (GMPs) and a general bias towards granulocyte formation (Wu et al, 2014). In addition, elevated numbers of circulating HSPCs correlate with tumor progression and decreased overall survival (Wildes et al, 2019; Wu et al, 2014). Moreover, it has been suggested that tumor-mediated signals directly affect the fate of HSPCs, leading to their differentiation into MDSCs that help forming a premetastatic niche (Gabrilovich et al, 2012; Wang et al, 2019).…”

Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas

“…1A). This combinatorial strategy strongly modulates the tumor microenvironment and promotes continued intratumor T-cell activation [29][30][31][32].…”