Abstract
Ineffective antigen cross-presentation in the tumor microenvironment compromises the generation of antitumor immune responses. Radiotherapy-radiodynamic therapy (RT-RDT) with nanoscale metal-organic frameworks (nMOFs) induces robust adaptive immune responses despite modest activation of canonical antigen presenting dendritic cells. Here, using transplantable and autochthonous murine tumor models, we demonstrate that RT-RDT induces antitumor immune responses via early neutrophil infiltration and reprogramming. Intravenous or intratumoral injection of nMOFs recruited peripheral CD11b+Ly6G+CD11c- neutrophils into tumors. The activation of nMOFs by low-dose X-rays significantly increased the population of CD11b+Ly6G+CD11c+ hybrid neutrophils with upregulated expression of the co-stimulatory molecules CD80 and CD86 as well as major histocompatibility complex class II molecules. Thus, nMOF-enabled RT-RDT reshapes a favorable tumor microenvironment for antitumor immune responses by reprogramming tumor-infiltrating neutrophils to function as non-canonical antigen presenting cells for effective cross-presentation of tumor antigens.
Original language | English (US) |
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Pages (from-to) | 17515-17527 |
Number of pages | 13 |
Journal | ACS Nano |
Volume | 15 |
Issue number | 11 |
DOIs | |
State | Published - Nov 23 2021 |
Keywords
- antitumor immunity
- autochthonous tumor model
- nanoscale metal-organic framework
- neutrophil reprogramming
- radiodynamic therapy
- radiotherapy
- tumor microenvironment
ASJC Scopus subject areas
- General Materials Science
- General Engineering
- General Physics and Astronomy