A malignant subpopulation of H2AFZ+ cells interacts with myeloid cells to promote an anti-inflammatory microenvironment and drive hepatic metastasis, revealing an immunotherapeutic strategy for pancre
5 hours ago
- #Pancreatic Cancer
- #Metastasis
- #Immunotherapy
- Hepatic metastasis is the primary cause of death in pancreatic ductal adenocarcinoma (PDAC).
- A metastasis-prone malignant subpopulation (H2AFZ+ cells) was identified, linked to higher metastasis risk and a transitional plastic state.
- This subpopulation exhibits a poorly differentiated, highly proliferative phenotype, with H2AFZ potentially driving this behavior.
- Hepatic metastases (HMs) show increased M2 macrophages, regulatory T cells, and exhausted T cells, indicating an immune-suppressive microenvironment.
- Exhausted T cells in HMs overexpress PDCD1 and LAG3, suggesting potential immunotherapeutic targets.
- Combined therapy targeting PDCD1 and LAG3 effectively inhibited tumor growth in metastatic PDAC mouse models.
- Findings reveal a metastasis-associated subpopulation and propose a promising immunotherapeutic strategy for metastatic PDAC.