Journal
CANCER IMMUNOLOGY RESEARCH
Volume 8, Issue 9, Pages 1193-1205Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0789
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Funding
- National Natural Science Foundation of China [81788101, 81530080, 91742112]
- CAMS Initiative for Innovative Medicine [2016-I2M-1-007]
- Young Elite Scientists Sponsorship Program by CAST [YESS20160166]
- Program for HUST Academic Frontier Youth Team [2018QYTD01]
- National Major Science and Technology Projects of China [2019ZX09301001]
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Malignant pleural effusion (MPE) is a frequent complication of various cancers and often leads to a poor quality of life, prognosis, and life expectancy, and its management remains palliative. New approaches that can effectively treat MPE are highly desirable. Here, we show that methotrexate ( MTX)-packaging tumor cell-derived microparticles (MTX-MP) act as an effective immunotherapeutic agent to treat patients with MPE by mobilizing and activating neutrophils. We find that MTX-MP perfusion via a pleural catheter elicits the recruitment of neutrophils in patients through macrophage-released CXCL1 and CXCL2. By performing ex vivo experiments, we find that the recruited neutrophils are activated and release reactive oxygen species ( ROS) and neutrophil extracellular trap (NET) to kill tumor cells. Neutrophil-released NETs were also able to seal off the damaged endothelium, facilitating MPE resolution in vitro and in tumor-bearing mice. These findings reveal the potential for use of cell- derived materials to package drugs as an immunotherapeutic agent against MPE.
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