Reprogramming of Neutrophils as Non-canonical Antigen Presenting Cells by Radiotherapy-Radiodynamic Therapy to Facilitate Immune-Mediated Tumor Regression.
Nining GuoKaiyuan NiTaokun LuoGuangxu LanAinhoa ArinaZiwan XuJianming MaoRalph R WeichselbaumMichael SpiottoWenbin LinPublished in: ACS nano (2021)
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.
Keyphrases
- immune response
- dendritic cells
- low dose
- induced apoptosis
- case report
- nk cells
- early stage
- radiation therapy
- squamous cell carcinoma
- toll like receptor
- cell cycle arrest
- high dose
- metal organic framework
- stem cells
- signaling pathway
- locally advanced
- mesenchymal stem cells
- cell death
- high resolution
- rectal cancer
- bone marrow
- high speed