Albumin-Bound STING Agonist Reprograms HSPCs to Antitumor Neutrophils Enhancing CD8+ T Cell Immunity - PubMed
2 hours ago
- #antitumor neutrophils
- #STING agonist
- #cancer immunotherapy
- Albumin-bound STING agonist (Nano ZSA-51D) reprograms hematopoietic stem and progenitor cells (HSPCs) to generate antitumor neutrophils.
- Reprogrammed neutrophils enhance MHC I-mediated CD8+ T cell immunity and sensitize tumors to α-PD1 immunotherapy.
- Nano ZSA-51D expands HSPCs and directs them toward granulocyte-monocyte progenitors for neutrophil development.
- Converts immature (CD101-) and mature (CD101+) neutrophils into a CD14+ICAM-1+ subset via STING-NF-κB-TNF-α signaling, improving tumor infiltration and antitumor activity.
- These neutrophils upregulate interferon signaling and MHC I antigen presentation, boosting tumor-specific CD8+ T cell responses.
- Adoptive transfer of reprogrammed neutrophils or systemic Nano ZSA-51D treatment synergizes with α-PD1 therapy, achieving complete remission in colon tumors and efficacy in pancreatic cancer models.
- Highlights potential of targeting early hematopoiesis to rewire neutrophil fate in cancer immunotherapy.