Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.

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BALB/C mice, female, 6-8 weeks were purchased from Harlan. The animals were hosted in equipped animal facility with temperature at 68-79 F and humidity at 30%-70%, under the same dark/light cycle (12:12).
No wild animals were used No filed-collection All animal experiments were performed under a National Institutes of Health Animal Care and Use Committee (NIHACUC) approved protocol.
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nature research | reporting summary
April 2020

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For tissue samples, tissues were mechanically disrupted and collected from mice. Then, the isolated tissues were cut into pieces and washed with cold staining buffer several times to obtain the single cell suspensions. Digestive enzyme (Collagenase IV (1 mg/mL)) was added for 6 h. The cell suspension was filtered through a 70-"m cell strainer to remove undegraded tissues. ACK lysis buffer (Ggbco) was added into the cell suspension. After 10 min, the single cell suspension was washed with flow cytometry buffer and then stained with the indicated antibodies.