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Hepatic hematopoiesis hijacked by tumor metastasis promotes immunosuppression

ABSTRACT: Cancer-associated hematopoietic abnormalities contribute to systemic immunosuppression. However, whether tumors can initiate localized extramedullary hematopoiesis (EMH) to suppress anti-tumor immunity remains unclear. Here, we identify a distinct form of hepatic hematopoiesis driven by liver metastasis-associated hematopoietic stem cells (LM-HSCs). Liver metastases establish ectopic periportal hematopoietic niches that recruit bone marrow HSCs through Kupffer cell-dependent CCR1 signaling. Although LM-HSCs retain self-renewal and multipotency, CREB activation skews their differentiation toward the myeloid lineage, particularly ANXA1⁺ immature neutrophils. These neutrophils produce glucocorticoids, which activate glucocorticoid receptor (GR) signaling in a paracrine manner and induce immune checkpoint receptor expression and functional anergy in CD8⁺ T and NK cells. Collectively, these findings demonstrate that liver metastases reprogram hepatic hematopoiesis to promote immunosuppression.

ORGANISM(S): Mus musculus

PROVIDER: GSE291385 | GEO | 2026/08/21

REPOSITORIES: GEO

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