Related Experiment Video
Updated: Jul 30, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis
Duo Wang1,2, Guanhua Qiu1,2, Xiaoqi Zhu1,2
1Department of Medical Ultrasound, Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
Background:
Immunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.
Methods:
To address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype macrophages. The delivered RSL3 that serves as a common ferroptosis inducer can reduce the levels of ferroptosis hallmarkers (eg, glutathione and glutathione peroxidase 4), break the redox homeostasis to magnify oxidative stress accumulation, promote the expression of ferroptosis-related proteins, and induce robust ferroptosis of tumor cells, accompanied with which systematic immune response activation can bbe realized. M1 macrophage-derived exosomes can inherit more functions and genetic substances than nanovesicles since nanovesicles inevitably suffer from substance and function loss caused by extrusion-arised structural damage.
Results:
Inspired by it, spontaneous homing to tumor and M2-like macrophage polarization into M1-like ones are attained, which not only significantly magnify oxidative stress but also mitigate ITM including M2-like macrophage polarization and regulatory T cell decrease, and regulate death pathways.
Conclusions:
All these actions accomplish a synergistic antitumor enhancement against tumor progression, thus paving a general route to mitigate ITM, activate immune responses, and magnify ferroptosis.
